There are numerous factors which seem to determine how each patient will respond.
If patients are to improve I believe that doctors need to try different approaches. The one size fits all method works poorly. A 43 year old woman was seen several months ago for a second opinion. She was diagnosed with fibromyalgia and CFS. She had been very physically active. She was a personal trainer. Now she was a wreck. She had typical signs and symptoms of disseminated Lyme and neuroborreliosis. Her SPECT showed left frontal lobe hypo perfusion. The brain MRI was normal. Her exam had neurological abnormalities and her labs confirmed exposure to Lyme. She was treated with Ceftin and Minocin. There was a tolerance issue and a bad Herx. She was given a Medrol dose pack and switched to Biaxin and Plaquenil. After two months she felt even worse. We started IV Rocephin. The pain was improving but the cognitive issues were unaffected. Symptoms of sweating in cycles suggested Babesiosis. Mepron and Artemesin were added(the Biaxin and Plaqueil had never been discontinued). The sweating went away but otherwise she felt worse.She only took this regimen for a month. There was a worsening of cognitive functions- more memory loss, and an increase in neuropathic symptoms and pain. She was then treated with only Rocephin: still not better. IV Zithromax was added- then she started to improve. It was the IV Zithromax that was making a difference. The Rocephin was stopped and she continued to improve. When Flagyl was added she again felt worse. The treatment was changed: IV Zithromax. Just Rifampin was added and she was now really improving. She was tired- but able to work. Her cognitive dysfunction was clearing up. Much of her pain was gone. (I had prescribed Levaquin but she didn't take it after looking up its side effects). I saw her today 5 months into treatment. The hangdog look was gone. She agreed to try the Levaquin. I hope it helps.
She had Lyme with neurocognitive deficits and an abnormal SPECT scan.
The only lab data I will add is that she had a high C6 Lyme peptide index and that her blood smear at Clongen showed motile gram negative coccobacilli.
What have I been treating her for?
Do people really have Herx reactions which go on for months?
If a patient Herxes for more than one month I think it is time to change the treatment. The immunological consequences of a prolonged "Herx" can't be good.
Bacteremic. Yes. With what? Has Fry found the answer before Clongen: We shall see.
Babesia- or an immitator like Toxoplasmosis, as exists in immunosupressed HIV patients? This has been suggested as a possibility.
Is there really Bartonella and or Mycoplasm. We don't know.
Why didn't Rocephin work while Zithromax did?
There are lots of questions and still few answers.
As a clinician all I can do is report my clinical results.
Again, one size does not fit all.
Wednesday, November 26, 2008
Tuesday, November 25, 2008
Sexual transmission
A single patient who is CDC positive for Lyme, symptomatic and off antibiotics for four months agreed to have his semen tested. An ultrasensitive culture was performed at Clongen labs. Diptheroids, thought to be a contaminant grew. No Borrelia grew in the culture medium. This is only one case. So far there is no evidence to support the theory that LD is sexually transmitted. Quack watch has criticized "LLMDS" for promoting this notion, well....
DNA fingerprinting has been difficult: Clongen still expects a answer soon? Perhaps next week: we shall see.
DNA fingerprinting has been difficult: Clongen still expects a answer soon? Perhaps next week: we shall see.
Monday, November 24, 2008
Towards a unified perspective
As confusing as Lyme disease is for patients; it is more confusing for me. As I became indoctrinated into the world of "Lyme literacy" it became easy to say/think that all the text books(and doctors) are wrong- Lyme is the cause of all the ill's of the world- why can't you blind doctors see that?. If one finds himself in such a manic state he either needs to take a Xanax, or slow down- take a deep breath, and look again. Are all the rheumatologists and neurologists wrong? Have I lost my mind. Can I be so pompous as to believe that only folks who think like me are right and that everyone else is wrong? (Lets leave infectious disease physicians out for the time being.) There are a "zillion" articles and texts which validate the paradigms they work under. Perhaps a more humble approach is needed. Perhaps everyone is a little right (and a little wrong). The more you are a hammer, the more everything around you takes on characteristics of nails.
At the core is the concept of inflammation. Inflammation is primarily an immunological response. The inflammatory process always begins when a foreign protein is introduced to the body. This is called an antigen. The sentries of the immune system, such as macrophages, sniff out the protein that doesn't belong. This leads to a complex process in which the immune system becomes activated. Without this process we could not survive. Not only does the immune system remove germs: its myriad functions include responding to allergens (proteins to which we have allergic responses) and even removing mutated cells, which if left unchecked could develop into cancer. Without this system we would be doomed. The system cannot be too efficient, it has to be quite selective. It has to recognize normal tissues and leave them undisturbed- we know this is not always the case; it even has to recognize "friendly" bacteria and other microbes, such as those that live in our gut. It has to be an awfully "smart" system.
If the immune system operates normally, things are kept in a state of equilibrium. If it is over activated we can become sick. Many checks and balances are in place- there is a delicate balance required for "normal" health. Sometimes, something very small- like an infection, can disturb the natural order and make us ill. I will confine my remarks to the imbalances caused by small micro-organisms known as bacteria.
When undesirable germs (we are speaking of bacteria here) enter the body the macrophages "gobble" them up. They are processed through the lens of histocompatibility complexes and presented to cells called helper T cell lymphocytes. These T cells somehow "read" the proteins on the surface of these antigens and transmit the information to B cell lymphocytes. These B cells quickly get to work, becoming factory which makes antibodies- special proteins called immunoglobulins, which are able to attach to germs and mark them for destruction. A vigorous response may be needed with alarm bells rung. The B cells can morph into monocytes which are even better antibody (immunoglobulin) factories. Quickly the macrophages and other immune cells crank out other immune system proteins called cytokines, which mobilize the natural immune processes. The cytokines are messenger proteins known as hormones. One can visualize the cytokines as traffic cops frantically directing speeding traffic coming from all directions-performed with pinpoint precision. While this process occurs at "light speed," A complex symphony of players melds into one. The complement system is activated. Special proteins are produced through a complex cascade which also directly attack the offending bacteria. Special proteins are released in very specific ways. Some of these are called: chemokines, bradykin, interleukins, tumor necrosis factor and interferons ( the last three are considered cytokines) and many other molecules. At this time more than 100 distinct cytokines have been discovered. So call "acute phase reactants" are released. These include C-reactive protein of which many of us are familiar. Then granulocytes move in. These are the big guns which gobble up and digest those doomed germs or antigens which have been marked for destruction. In the process granuals are released shedding other inflammatory proteins such as histamine, prostaglandins and leukotriones. The inflammatory process affects many tissues. For example, it affects the lining of the blood vessels, the endothelium, leading to the leaking of fluids (serum) into the surrounding areas. Nitrous oxide is released which promotes an inflammatory response. There is an increase in the clotting pathways of blood proteins. Of course the story is much more complex than this.
Since perhaps millions of pages have been written about the above topic, keep in mind that this represents a vast oversimplification, and that the author is a simple country doctor- trying hard to make sense of a disease many of my colleagues insist does not exist.
How are all these proteins made? They are made in cellular structures called ribosomes of which you have heard much. The ribosomes in our cells, (eucariotic) are quite different from those in bacteria, (procariotic). Antibiotics know which ones to attack. Protein synthesis in each case is directed by RNA, which comes directly from DNA, the blueprint for everything that transpires in our bodies.
Like everything in the universe: the immune system if not infallible. Sometimes mistakes are made.
Let us turn our attention to what rheumatologist know. They actually know quite a lot. They know that variations in histocompatibility complexes, genetically mediated, are associated with various illnesses. These genes have names like: DR and DQ. Small mutations in these genes are associated with differing autoimmune diseases.
Numerous auto-antibodies have been discovered. Theses include rheumatoid factor, ANA, Anti-Sm, Anti-RPN, Anti-Ro, Anti-La and numerous others. These antibodies have special relevance with regard to well characterized rheumatological disorders. Autoimmune disorders are defined based on various clinical and laboratory criteria. There is a great deal of overlap. Symptoms from column A and antibodies from column B are combined in various complex ways to make the diagnosis. Lupus, rheumatoid arthritis and scleroderma constitue only a small fraction of these varied autoimmune disorders. Sometimes these disorders are broken down into those which respond to steroids and those which do not. Rheumatologists and rheumatological literature prominently claims that these disorders are of unknown cause.
Now let us take a look at what rheumatologists have forgotten.
Rheumatic fever is a autoimmune rheumatolgical disorder. It occurs after a Streptoccal infection, usually in the throat (pharyx). It occurs some time after the initial infection. It is an autoimmune disorder because it affects organs which are distant from the site of infection. Typically in affects the skin, the joints, the heart, the kidneys and the brain. Although early treatment generally prevents its occurrence, it can occur despite the lack of signs of ongoing Strep infection (the infections may be considered occult) Recurrent or persistent infection is associated with a relapse of the disease. In some cases indefinite use of antibiotics is recommended to prevent recurrence of the disease.
Another disease associated with Strep infection goes by the name PANDAS. This is an autoimmune disorder affecting the brains of children. It is associated with occult Strep infection. The sufferers have psychiatric symptoms including obsessive compulsive disorder and tics(not ticks). Patients can frequently be taken off psychotropic medication and successfully treated with antibiotics.
Many disorders diagnosed by rheumatologists are called reactive. They follow an infection. The paradigm is that the infection has resolved but that an autoimmune disorder, triggered by the infection remains. Rheumatologic sources point to evidence that continued antibiotic therapy does not influence the outcome. What have they forgotten?
Continued antibiotic therapy does influence the course of rheumatic fever and PANDAS.
Let us consider a little microbiology. Strep is an easy germ to kill. It has no known ability to develop resistance to antibiotics; it replicates quickly and it does not form spores.
How about rheumatoid arthritis? Studies have demonstrated M. fermantans in the synovial fluid of patients with RA. This has been confirmed by 16S rDNA. Viable organisms have also been demonstrated in the synovial tissues. Treatment with antibiotics hasn't helped- or has it. Numerous studies show that Doxycyline and Minocyline are in fact effective drugs for RA. I have observed that rheumatologists tend to avoid these drugs preferring agents which are much more toxic in my opinion.
And unlike the case with Strep- Mycoplasmas are very difficult to eradicate.
Inflammation is bad- so we are constantly told. It in the media all the time. C-reactive protein is a stronger indicator of heart attack risk than cholesterol measurements. Chlamydia pneumonia and other bacteria have been shown to be present in atherosclerotic plaques inside the walls of arteries which can rupture and lead to heart attack and stroke. Some studies have been with drugs like Doxycyline. Is this going to work? Stratton has shown that this organism is very resistant to eradication and that complex multi-drug regimens are needed.
Let us go full circle. Why are people sick who have contracted Lyme disease? We know the causative germ is invasive and nearly impossible to eradicate. We know patients have co-infections which aggravate the disease. Still, some folks who are infected remain relatively unaffected. They are mildly ill or altogether well. The immune response must be a key part of this mystery. For example, the most commonly measured autoimmune antibody is the rheumatoid factor. This is an IgM antibody directed against IgG antibodies. IgM antibodies represent the acute response to an infection. They are made quickly but are not all that effective. In general, they should be supplanted by the more effective, second phase IgG antibodies. Some physicians are troubled by the fact that so called chronic Lyme patients primarily have an IgM response, not an IgG response. If the disease were chronic they reason, one should see IgG responses in the blood. (Actually it turns out that patients who have a robust IgG response to Lyme infection are healthier and respond better to treatment). Is this logical? IgG responses indicate a full immunological/antibody response. These responses are seen in patients who are no longer ill but are in fact recovering from an infectious disease. These are smaller antibodies which bind better to the target sites. So this is not the response one would expect to see in patients with chronic Lyme disease- if such an entity does indeed exist? If the infection is active one would expect IgM antibodies- there is active inflammation. Is this not analagous to the phenomenon which observed with rheumatoid arthritis? Remember, the rheumatoid factor is an IgM antibody. The sickest Lyme patients in fact never have a good IgG response. For some reason the sickest patients are unable to mount a protective immune response. Such patients may suffer and endless cycle of infection and inflammation which becomes very difficult to treat.
And what do we see in chronic Lyme patients? They have an increased incidence of autoimmune antibodies. They have elevated CRP and sed rates. They have elevated complement levels including C3a, C3b and C4a. They have increased circulating immune complexes. They have increased levels of cytokines. They experience inflammatory hematologic abnormalities: the white blood cell count is low. An increased, lymphocyte response may be present, platelet levels may be decreased and abnormalities of blood coagulation may be seen. Alterations in vitamin B12, folic acid and vitamin D may correspond to an active inflammatory process.
Is it post Lyme syndrome? Are the germs gone and we are simply seeing an autoimmune disorder as suggested by the IDSA? This begs the question: What are autoimmune disorders? We have seen evidence that they are in fact promoted by ongoing infection. Autoimmune disorders occur because auto-antibodies are produced. Antibodies are produced when macrophages are activated by foreign proteins. For some yet unexplained reason, sometimes auto-antibodies are produced rather than normal antibodies which would target the offending antigen(protein). The distaff argument then becomes, auto-antibodies are produced because memory cells are activated. When B cells and plasma cells "learn" how to make a particular antibody memory cells are created. These cells "remember" how to make the antibodies and quickly kick into gear when the offending antibody is present. This is why vaccines work. However, there is no reason to believe that these memory cells make antibodies spontaneously. It makes sense that the process is triggered by new antigen exposure. This would explain for example, why rheumatic fever flares up with new exposure to Streptococcal bacteria. The immune system is activated by continued exposure to antigen. In Lyme disease, this dovetails with the observation that IgM antibodies predominate. The immune pump is constantly being primed. I would suggest that a theory of autoimmune disease should include the notion of repeated antigenic stimulation and therefore persistent infection. There is good experimental evidence that patients with "autoimmune" disease, such as rheumatoid arthritis, do in fact show persistent infection.
What do rheumatologist do with their patients? They use steroids. These medications are immunosuppressive. They damp down the entire immune cascade. They reduce activity of macrophages, lymphocytes, granulocytes and cytokines. Patients certainly feel better. The underlying infections may be unchecked with an undesirable effect.
Patients with Lyme who are pregnant feel better. Pregnancy is associated with an immunsuppressed state. After delivery the patients generally have severe relapses as the immune system returns to baseline. Rheumatologists typically prescribe a wide array of immune suppressing drugs. These medications have serious side effects such as life threatening infections and cancers. Concerns regarding the overuse of antibiotics seem less significant in this context.
Are antibiotics bad? Readers of my blog seem very preoccupied with this question.
Antibiotics are neither good nor bad. They are very useful tools essential to the treatment of disorders such as chronic Lyme disease.
A second question is: are alternative and complementary therapies bad? I am concerned about this issue. Many patients who use such therapies claim they help; however, the same patients speak about chronic suffering- the implication: Lyme disease cannot be cured. I am concerned that a focus on these therapies can deprive patients of more effective therapies which offer improvement and a high likelihood of long term remission.
Severe Lyme disease is very bad and must be treated with the most effective tools at our disposal.
Are there ways to make the immune system work better? This question is oft raised. At this time there are no great answers. But perhaps there may be some clues. The relaxation response improves immune function. Exercise improves immune function. A positive mental attitude improves immune function. Correction of sleep disturbances, especially sleep apnea improves immune function. Not being obese improves immune function. Certain diets may improve immune function. Gluten sensitivity and food allergies may stress the immune system and compound the effects of Lyme disease. It is possible that a stressed immune system may experience a tipping point. Removing some of those stressors may allow for quicker overall healing.
What about vitamins and supplements? I am not convinced, sorry. Vitamin A deficiency can cause a decrement in immune responses- but do not take this- it is fat soluble and can be toxic. What about vitamin D. Lately I have given this some thought. In the past I have espoused the belief that vitamin D dysregulation is a pathogen induced process which increases the survival of intracellular pathogens. This theory came from my reading of Marshall's theories. Perhaps this is completely wrong. Another possibility is that vitamin D levels are raised not by the bacteria, but by the host. Perhaps this is an adaptive response to damp down an exuberant immune response which the host senses is causing harm to our bodies. I will stop criticizing doctors who give LD patients D. For now I don't know, and I will leave this topic alone.
All of these ramblings- and not once have I mentioned the helper cell Th1 versus Th2 controversy. This issue has received too much press. The same can be said for the natural killer T cell issue. These immune cells are probably down regulated by a cytokine response. But I have not found the CD57 marker to offer clinical benefit.
Let me finally return to the title of this entry: Towards a unified perspective.
Rheumatologists are right in their characterization of autoimmune disorders. They claim that the cause of such disorders remains unknown. I am simply suggesting that one can take the process back a notch, and posit that the precipitating causes are infection(s), of which Borrelia burdorferi- the Lyme bacteria may be one. And to the neurologists who asked me: "Are you trying to tell me the patient has Lyme disease, not MS." My response would be the same. MS is a well characterized autoimmune disorder associated with destruction of the protective myelin sheath of neurons. You say it is of unknown cause. I am simply offering a theory which provides an explanation of the underlying cause. Such an explanation may also offer therapeutic considerations. So you see- we can all agree, can't we?
As I said early on- I am omitting infectious disease specialists for the time being.
At the core is the concept of inflammation. Inflammation is primarily an immunological response. The inflammatory process always begins when a foreign protein is introduced to the body. This is called an antigen. The sentries of the immune system, such as macrophages, sniff out the protein that doesn't belong. This leads to a complex process in which the immune system becomes activated. Without this process we could not survive. Not only does the immune system remove germs: its myriad functions include responding to allergens (proteins to which we have allergic responses) and even removing mutated cells, which if left unchecked could develop into cancer. Without this system we would be doomed. The system cannot be too efficient, it has to be quite selective. It has to recognize normal tissues and leave them undisturbed- we know this is not always the case; it even has to recognize "friendly" bacteria and other microbes, such as those that live in our gut. It has to be an awfully "smart" system.
If the immune system operates normally, things are kept in a state of equilibrium. If it is over activated we can become sick. Many checks and balances are in place- there is a delicate balance required for "normal" health. Sometimes, something very small- like an infection, can disturb the natural order and make us ill. I will confine my remarks to the imbalances caused by small micro-organisms known as bacteria.
When undesirable germs (we are speaking of bacteria here) enter the body the macrophages "gobble" them up. They are processed through the lens of histocompatibility complexes and presented to cells called helper T cell lymphocytes. These T cells somehow "read" the proteins on the surface of these antigens and transmit the information to B cell lymphocytes. These B cells quickly get to work, becoming factory which makes antibodies- special proteins called immunoglobulins, which are able to attach to germs and mark them for destruction. A vigorous response may be needed with alarm bells rung. The B cells can morph into monocytes which are even better antibody (immunoglobulin) factories. Quickly the macrophages and other immune cells crank out other immune system proteins called cytokines, which mobilize the natural immune processes. The cytokines are messenger proteins known as hormones. One can visualize the cytokines as traffic cops frantically directing speeding traffic coming from all directions-performed with pinpoint precision. While this process occurs at "light speed," A complex symphony of players melds into one. The complement system is activated. Special proteins are produced through a complex cascade which also directly attack the offending bacteria. Special proteins are released in very specific ways. Some of these are called: chemokines, bradykin, interleukins, tumor necrosis factor and interferons ( the last three are considered cytokines) and many other molecules. At this time more than 100 distinct cytokines have been discovered. So call "acute phase reactants" are released. These include C-reactive protein of which many of us are familiar. Then granulocytes move in. These are the big guns which gobble up and digest those doomed germs or antigens which have been marked for destruction. In the process granuals are released shedding other inflammatory proteins such as histamine, prostaglandins and leukotriones. The inflammatory process affects many tissues. For example, it affects the lining of the blood vessels, the endothelium, leading to the leaking of fluids (serum) into the surrounding areas. Nitrous oxide is released which promotes an inflammatory response. There is an increase in the clotting pathways of blood proteins. Of course the story is much more complex than this.
Since perhaps millions of pages have been written about the above topic, keep in mind that this represents a vast oversimplification, and that the author is a simple country doctor- trying hard to make sense of a disease many of my colleagues insist does not exist.
How are all these proteins made? They are made in cellular structures called ribosomes of which you have heard much. The ribosomes in our cells, (eucariotic) are quite different from those in bacteria, (procariotic). Antibiotics know which ones to attack. Protein synthesis in each case is directed by RNA, which comes directly from DNA, the blueprint for everything that transpires in our bodies.
Like everything in the universe: the immune system if not infallible. Sometimes mistakes are made.
Let us turn our attention to what rheumatologist know. They actually know quite a lot. They know that variations in histocompatibility complexes, genetically mediated, are associated with various illnesses. These genes have names like: DR and DQ. Small mutations in these genes are associated with differing autoimmune diseases.
Numerous auto-antibodies have been discovered. Theses include rheumatoid factor, ANA, Anti-Sm, Anti-RPN, Anti-Ro, Anti-La and numerous others. These antibodies have special relevance with regard to well characterized rheumatological disorders. Autoimmune disorders are defined based on various clinical and laboratory criteria. There is a great deal of overlap. Symptoms from column A and antibodies from column B are combined in various complex ways to make the diagnosis. Lupus, rheumatoid arthritis and scleroderma constitue only a small fraction of these varied autoimmune disorders. Sometimes these disorders are broken down into those which respond to steroids and those which do not. Rheumatologists and rheumatological literature prominently claims that these disorders are of unknown cause.
Now let us take a look at what rheumatologists have forgotten.
Rheumatic fever is a autoimmune rheumatolgical disorder. It occurs after a Streptoccal infection, usually in the throat (pharyx). It occurs some time after the initial infection. It is an autoimmune disorder because it affects organs which are distant from the site of infection. Typically in affects the skin, the joints, the heart, the kidneys and the brain. Although early treatment generally prevents its occurrence, it can occur despite the lack of signs of ongoing Strep infection (the infections may be considered occult) Recurrent or persistent infection is associated with a relapse of the disease. In some cases indefinite use of antibiotics is recommended to prevent recurrence of the disease.
Another disease associated with Strep infection goes by the name PANDAS. This is an autoimmune disorder affecting the brains of children. It is associated with occult Strep infection. The sufferers have psychiatric symptoms including obsessive compulsive disorder and tics(not ticks). Patients can frequently be taken off psychotropic medication and successfully treated with antibiotics.
Many disorders diagnosed by rheumatologists are called reactive. They follow an infection. The paradigm is that the infection has resolved but that an autoimmune disorder, triggered by the infection remains. Rheumatologic sources point to evidence that continued antibiotic therapy does not influence the outcome. What have they forgotten?
Continued antibiotic therapy does influence the course of rheumatic fever and PANDAS.
Let us consider a little microbiology. Strep is an easy germ to kill. It has no known ability to develop resistance to antibiotics; it replicates quickly and it does not form spores.
How about rheumatoid arthritis? Studies have demonstrated M. fermantans in the synovial fluid of patients with RA. This has been confirmed by 16S rDNA. Viable organisms have also been demonstrated in the synovial tissues. Treatment with antibiotics hasn't helped- or has it. Numerous studies show that Doxycyline and Minocyline are in fact effective drugs for RA. I have observed that rheumatologists tend to avoid these drugs preferring agents which are much more toxic in my opinion.
And unlike the case with Strep- Mycoplasmas are very difficult to eradicate.
Inflammation is bad- so we are constantly told. It in the media all the time. C-reactive protein is a stronger indicator of heart attack risk than cholesterol measurements. Chlamydia pneumonia and other bacteria have been shown to be present in atherosclerotic plaques inside the walls of arteries which can rupture and lead to heart attack and stroke. Some studies have been with drugs like Doxycyline. Is this going to work? Stratton has shown that this organism is very resistant to eradication and that complex multi-drug regimens are needed.
Let us go full circle. Why are people sick who have contracted Lyme disease? We know the causative germ is invasive and nearly impossible to eradicate. We know patients have co-infections which aggravate the disease. Still, some folks who are infected remain relatively unaffected. They are mildly ill or altogether well. The immune response must be a key part of this mystery. For example, the most commonly measured autoimmune antibody is the rheumatoid factor. This is an IgM antibody directed against IgG antibodies. IgM antibodies represent the acute response to an infection. They are made quickly but are not all that effective. In general, they should be supplanted by the more effective, second phase IgG antibodies. Some physicians are troubled by the fact that so called chronic Lyme patients primarily have an IgM response, not an IgG response. If the disease were chronic they reason, one should see IgG responses in the blood. (Actually it turns out that patients who have a robust IgG response to Lyme infection are healthier and respond better to treatment). Is this logical? IgG responses indicate a full immunological/antibody response. These responses are seen in patients who are no longer ill but are in fact recovering from an infectious disease. These are smaller antibodies which bind better to the target sites. So this is not the response one would expect to see in patients with chronic Lyme disease- if such an entity does indeed exist? If the infection is active one would expect IgM antibodies- there is active inflammation. Is this not analagous to the phenomenon which observed with rheumatoid arthritis? Remember, the rheumatoid factor is an IgM antibody. The sickest Lyme patients in fact never have a good IgG response. For some reason the sickest patients are unable to mount a protective immune response. Such patients may suffer and endless cycle of infection and inflammation which becomes very difficult to treat.
And what do we see in chronic Lyme patients? They have an increased incidence of autoimmune antibodies. They have elevated CRP and sed rates. They have elevated complement levels including C3a, C3b and C4a. They have increased circulating immune complexes. They have increased levels of cytokines. They experience inflammatory hematologic abnormalities: the white blood cell count is low. An increased, lymphocyte response may be present, platelet levels may be decreased and abnormalities of blood coagulation may be seen. Alterations in vitamin B12, folic acid and vitamin D may correspond to an active inflammatory process.
Is it post Lyme syndrome? Are the germs gone and we are simply seeing an autoimmune disorder as suggested by the IDSA? This begs the question: What are autoimmune disorders? We have seen evidence that they are in fact promoted by ongoing infection. Autoimmune disorders occur because auto-antibodies are produced. Antibodies are produced when macrophages are activated by foreign proteins. For some yet unexplained reason, sometimes auto-antibodies are produced rather than normal antibodies which would target the offending antigen(protein). The distaff argument then becomes, auto-antibodies are produced because memory cells are activated. When B cells and plasma cells "learn" how to make a particular antibody memory cells are created. These cells "remember" how to make the antibodies and quickly kick into gear when the offending antibody is present. This is why vaccines work. However, there is no reason to believe that these memory cells make antibodies spontaneously. It makes sense that the process is triggered by new antigen exposure. This would explain for example, why rheumatic fever flares up with new exposure to Streptococcal bacteria. The immune system is activated by continued exposure to antigen. In Lyme disease, this dovetails with the observation that IgM antibodies predominate. The immune pump is constantly being primed. I would suggest that a theory of autoimmune disease should include the notion of repeated antigenic stimulation and therefore persistent infection. There is good experimental evidence that patients with "autoimmune" disease, such as rheumatoid arthritis, do in fact show persistent infection.
What do rheumatologist do with their patients? They use steroids. These medications are immunosuppressive. They damp down the entire immune cascade. They reduce activity of macrophages, lymphocytes, granulocytes and cytokines. Patients certainly feel better. The underlying infections may be unchecked with an undesirable effect.
Patients with Lyme who are pregnant feel better. Pregnancy is associated with an immunsuppressed state. After delivery the patients generally have severe relapses as the immune system returns to baseline. Rheumatologists typically prescribe a wide array of immune suppressing drugs. These medications have serious side effects such as life threatening infections and cancers. Concerns regarding the overuse of antibiotics seem less significant in this context.
Are antibiotics bad? Readers of my blog seem very preoccupied with this question.
Antibiotics are neither good nor bad. They are very useful tools essential to the treatment of disorders such as chronic Lyme disease.
A second question is: are alternative and complementary therapies bad? I am concerned about this issue. Many patients who use such therapies claim they help; however, the same patients speak about chronic suffering- the implication: Lyme disease cannot be cured. I am concerned that a focus on these therapies can deprive patients of more effective therapies which offer improvement and a high likelihood of long term remission.
Severe Lyme disease is very bad and must be treated with the most effective tools at our disposal.
Are there ways to make the immune system work better? This question is oft raised. At this time there are no great answers. But perhaps there may be some clues. The relaxation response improves immune function. Exercise improves immune function. A positive mental attitude improves immune function. Correction of sleep disturbances, especially sleep apnea improves immune function. Not being obese improves immune function. Certain diets may improve immune function. Gluten sensitivity and food allergies may stress the immune system and compound the effects of Lyme disease. It is possible that a stressed immune system may experience a tipping point. Removing some of those stressors may allow for quicker overall healing.
What about vitamins and supplements? I am not convinced, sorry. Vitamin A deficiency can cause a decrement in immune responses- but do not take this- it is fat soluble and can be toxic. What about vitamin D. Lately I have given this some thought. In the past I have espoused the belief that vitamin D dysregulation is a pathogen induced process which increases the survival of intracellular pathogens. This theory came from my reading of Marshall's theories. Perhaps this is completely wrong. Another possibility is that vitamin D levels are raised not by the bacteria, but by the host. Perhaps this is an adaptive response to damp down an exuberant immune response which the host senses is causing harm to our bodies. I will stop criticizing doctors who give LD patients D. For now I don't know, and I will leave this topic alone.
All of these ramblings- and not once have I mentioned the helper cell Th1 versus Th2 controversy. This issue has received too much press. The same can be said for the natural killer T cell issue. These immune cells are probably down regulated by a cytokine response. But I have not found the CD57 marker to offer clinical benefit.
Let me finally return to the title of this entry: Towards a unified perspective.
Rheumatologists are right in their characterization of autoimmune disorders. They claim that the cause of such disorders remains unknown. I am simply suggesting that one can take the process back a notch, and posit that the precipitating causes are infection(s), of which Borrelia burdorferi- the Lyme bacteria may be one. And to the neurologists who asked me: "Are you trying to tell me the patient has Lyme disease, not MS." My response would be the same. MS is a well characterized autoimmune disorder associated with destruction of the protective myelin sheath of neurons. You say it is of unknown cause. I am simply offering a theory which provides an explanation of the underlying cause. Such an explanation may also offer therapeutic considerations. So you see- we can all agree, can't we?
As I said early on- I am omitting infectious disease specialists for the time being.
Friday, November 21, 2008
Odds and Ends
I don't use alternative therapies. Sometimes C.diff and other issues make standard therapy impractical. Patients can try protocols described by Buhner, Coweden and others. I have not found such therapies to be terribly effective in my patients. Salt and C: I don't use it. Anecdotal reports of its efficacy exist. This dove tails with one of the weirder aspects of the disease. Some patients with Lyme claims to see worms in their stool. It has been suggested that this is an unknown microfilaria species. Patients have in fact brought me stool specimens with visible worms. Labs have not IDed the organisms . The first thing the Willie Burdorfer saw in tick guts was worms. I don't know if this species has been characterized. High levels of Na in the gut may have an osmotic effect and act as a de-wormer as has been suggested by some. For such patient, Ivermectin has been tried. Sometimes it seems to help- I am reluctant to recommend this therapy at this time. Dr. Stricker who treat many Morgellons patients uses this anti-parasitic medication with some success. There is some connection between Morgellons and Lyme disease. This is outside my comfort zone.
My expertise(if I have any) has accrued over time. The combinations of drugs I used two years ago were more empiric then systematic. My approaches now are more regimented. I am not sure this has improved the results. For example, when I first read about LD treatments, I noted that Jemsek reported success with Cipro and Doxy. It didn't occur to me that I might also be treating "Bartonella." I used Rifampin because many patients reported that it had been effective; maybe this too was treating something other than Borrelia. The treatments were more hodgepodge. So when I review the cases of patients I have treated over time it may reflect an evolution in my general approach. It is still evolving.
IVIG sound great: I can't prescribe it because of standard of care limitations.
Invanz is a 24 hour drug with a broad spectrum of coverage. There are variable responses of drugs within the same class. I mentioned it based on one anecdote. It might be a great addition to the available arsenal. Most antibiotics require more complex dosing strategies. Unfortunately we have no data regarding the use of many antibiotics including this one.
Whether patients get very ill probably depends on a host of factors. Some strains of Bb may be more pathogenic. The mix of co-infections varies. Individual immunological responses based on genetics may play a large role. Some of this may be medicated by major histocompatibility molecules(genetically determined). Some patients only have IgM responses which made bode poorly versus those patients who develop a robust IgG response. So far we cannot do much about individual genetic based immune responses, but such things may have prognostic and or treatment value.
My expertise(if I have any) has accrued over time. The combinations of drugs I used two years ago were more empiric then systematic. My approaches now are more regimented. I am not sure this has improved the results. For example, when I first read about LD treatments, I noted that Jemsek reported success with Cipro and Doxy. It didn't occur to me that I might also be treating "Bartonella." I used Rifampin because many patients reported that it had been effective; maybe this too was treating something other than Borrelia. The treatments were more hodgepodge. So when I review the cases of patients I have treated over time it may reflect an evolution in my general approach. It is still evolving.
IVIG sound great: I can't prescribe it because of standard of care limitations.
Invanz is a 24 hour drug with a broad spectrum of coverage. There are variable responses of drugs within the same class. I mentioned it based on one anecdote. It might be a great addition to the available arsenal. Most antibiotics require more complex dosing strategies. Unfortunately we have no data regarding the use of many antibiotics including this one.
Whether patients get very ill probably depends on a host of factors. Some strains of Bb may be more pathogenic. The mix of co-infections varies. Individual immunological responses based on genetics may play a large role. Some of this may be medicated by major histocompatibility molecules(genetically determined). Some patients only have IgM responses which made bode poorly versus those patients who develop a robust IgG response. So far we cannot do much about individual genetic based immune responses, but such things may have prognostic and or treatment value.
Thursday, November 20, 2008
Ivanz- who knew
A new Lyme med?
This 48 year old female was not one of my best success stories. Despite this, I had helped her a great deal. Two years ago she came to me a train wreck. She had incapacitating total body pain, cognitive impairments and abdominal pain. She had seen rheumatologist who had treated her with immunomodulators including gold and prednisone. Nothing had helped. Antibiotics had caused strange reactions- numbness and tingling in her mouth. Numerous doctors had no idea what was causing her abdominal pain and myriad other symptoms. She had been sick for over 20 years and was at the end of her rope.
The abdominal pain was easy. I have found that gastroenterologists and surgeons make this same mistake over and over again. She had classic right upper quadrant abdominal pain with a tender gallbladder(positive Murphy sign). She had had numerous CT scans and ultrasounds which were negative. Her HIDA biliary scan was normal. The CCK injection given during the test reproduced her symptoms. This is key. If hormonal stimulation of the gallbladder reproduces the pain- the gallbladder is diseased. A clinical rule which has served me well over the years is simple: Treat the patient, not the labs or ancillary tests. The first surgeon I sent her to refused to consider surgery. She was an obvious hypochondriac. Besides, the GI specialists didn't think she had gallbladder disease: IBS. The second surgeon performed a laparoscopic cholecystectomy. Bingo. Path showed chronic cholecystitis.
In my experience, Lyme frequently causes gallbladder disease. She felt better and was impressed right off the bat that I had figured out one of the mysteries. Her labs made TBD a no brainer. She had positive Babesia serology from Labcorp. We began a long odyssey of treatment. There were ups and downs. Antibiotic side effects and intolerance led to long periods of no treatment. Symptoms invariably relapsed. The fibromyalgia and joint pains were somewhat refractory to therapy. Her cognitive improvements were steady. She suffered with bouts of serious depression which complicated her care. Along the way she had two courses of IV Rocephin. They were not as effective as I hoped they would be. Recently she came into my office very concerned. She told me that she had been coughing for two months- she smokes 2 packs per day- she knew that she had lung cancer. My intuition- its not cancer. The Chest Xray showed a mass. She was a wreck. I pointed out that it might be an infection. I ordered the CT, PET and a needle biopsy. The results were non-specific inflammation. No signs of cancer. It looked like a lung abscess. I thought it might be related to Bartonella. I started her on Cleocin and Levaquin. She collapsed in what looked like the mother of all Herxes. She was admitted to the hospital. She saw all the king's horses and all the king's men. They ultimately decided it was indeed a lung abscess. They were unable to identify a causative pathogen. The infectious disease doctor started her on Invanz. Its a new beta lactam antibiotic given once daily. It seems to kill everything that has a cell wall: gram positives, gram negatives and anerobes.
She was in the hospital for 6 days. Something magical happened. I saw her today. She was more bright and chipper than I had ever seen. There was almost a glow of wellness about her. This is the best she had felt in 20 years!. Virtually all of her symptoms had vanished.
Could this drug be a magic bullet that wipes out Lyme and the mystery bacteria crawling around in the bloodstreams of my patients?
Perhaps some other LLMDS should look at this and give it a try. I am trying to avoid more controversial therapies at the moment. This new antibiotics was only approved in the beginning of 2007.
PS: If it appears that I only write about my success stories it is because the other patients are a work in progress. I never give up- and neither do my patients.
This 48 year old female was not one of my best success stories. Despite this, I had helped her a great deal. Two years ago she came to me a train wreck. She had incapacitating total body pain, cognitive impairments and abdominal pain. She had seen rheumatologist who had treated her with immunomodulators including gold and prednisone. Nothing had helped. Antibiotics had caused strange reactions- numbness and tingling in her mouth. Numerous doctors had no idea what was causing her abdominal pain and myriad other symptoms. She had been sick for over 20 years and was at the end of her rope.
The abdominal pain was easy. I have found that gastroenterologists and surgeons make this same mistake over and over again. She had classic right upper quadrant abdominal pain with a tender gallbladder(positive Murphy sign). She had had numerous CT scans and ultrasounds which were negative. Her HIDA biliary scan was normal. The CCK injection given during the test reproduced her symptoms. This is key. If hormonal stimulation of the gallbladder reproduces the pain- the gallbladder is diseased. A clinical rule which has served me well over the years is simple: Treat the patient, not the labs or ancillary tests. The first surgeon I sent her to refused to consider surgery. She was an obvious hypochondriac. Besides, the GI specialists didn't think she had gallbladder disease: IBS. The second surgeon performed a laparoscopic cholecystectomy. Bingo. Path showed chronic cholecystitis.
In my experience, Lyme frequently causes gallbladder disease. She felt better and was impressed right off the bat that I had figured out one of the mysteries. Her labs made TBD a no brainer. She had positive Babesia serology from Labcorp. We began a long odyssey of treatment. There were ups and downs. Antibiotic side effects and intolerance led to long periods of no treatment. Symptoms invariably relapsed. The fibromyalgia and joint pains were somewhat refractory to therapy. Her cognitive improvements were steady. She suffered with bouts of serious depression which complicated her care. Along the way she had two courses of IV Rocephin. They were not as effective as I hoped they would be. Recently she came into my office very concerned. She told me that she had been coughing for two months- she smokes 2 packs per day- she knew that she had lung cancer. My intuition- its not cancer. The Chest Xray showed a mass. She was a wreck. I pointed out that it might be an infection. I ordered the CT, PET and a needle biopsy. The results were non-specific inflammation. No signs of cancer. It looked like a lung abscess. I thought it might be related to Bartonella. I started her on Cleocin and Levaquin. She collapsed in what looked like the mother of all Herxes. She was admitted to the hospital. She saw all the king's horses and all the king's men. They ultimately decided it was indeed a lung abscess. They were unable to identify a causative pathogen. The infectious disease doctor started her on Invanz. Its a new beta lactam antibiotic given once daily. It seems to kill everything that has a cell wall: gram positives, gram negatives and anerobes.
She was in the hospital for 6 days. Something magical happened. I saw her today. She was more bright and chipper than I had ever seen. There was almost a glow of wellness about her. This is the best she had felt in 20 years!. Virtually all of her symptoms had vanished.
Could this drug be a magic bullet that wipes out Lyme and the mystery bacteria crawling around in the bloodstreams of my patients?
Perhaps some other LLMDS should look at this and give it a try. I am trying to avoid more controversial therapies at the moment. This new antibiotics was only approved in the beginning of 2007.
PS: If it appears that I only write about my success stories it is because the other patients are a work in progress. I never give up- and neither do my patients.
Wednesday, November 19, 2008
17 month review
A 46 year old woman first came to me about 17 months ago. She had a history Lyme disease about 7 years before our first encounter. She had been treated with a three week course of Doxycycline. Her doctors over the years had diagnosed fibromyalgia, chronic fatigue syndrome and memory loss of unknown cause. She also had a history of unspecified colitis dating back 5 years. She was referred to me by a friend. On that occasion her symptoms included: headaches- severe, diffuse total body pain- severe, blurred vision, decreased hearing, memory loss, episodes of weakness and tingling of the extremities. She reported a prior history of Clostridia difficile colitis and an allergic reaction to Flagyl. This was reported to be a serum sickness like reaction and had caused a neurological reaction- some sort of muscle weakness. Her labs showed CDC positive Lyme antibodies. She was started on Ketek with probiotics. She had a massive Herx response. Plaquenil was added. She developed a urinary tract infection which led her to the hospital. Levaquin was given. Two months into treatment she saw improvements. Her hearing had improved. Her mental acuity was better. Her pain had decreased. A month later there was trouble. She developed some abdominal cramping, diarrhea and blood. She had chills. There was marked cognitive improvement. I was worried about C. diff and I knew she had a history of colitis. I had to stop antibiotics. With nothing else to offer, herbal therapy was recommended. One month later she was mostly better GI wise. The Lyme symptoms had neither worsened or improved. Asacol was started for colitic symptoms.
I was going through my experimental "CAM" phase. I even tried the vit C and Na protocol. It may have helped a "smidgen." Three months later I bit the bullet. Ramping up the probiotics she started Zithromax and Rifampin. No diarrhea. A herx: fatigue, increased numbness and now orthostatic dizziness. Adrenal insufficiency? I started low dose cortef, 5mg twice daily. Her insurance wouldn't cover Zithro and we switched to Biaxin. Now 5 months into treatment things were gradually improving. She had crawling sensations- saw worms in her stool and had small fibers extruding from her skin.(I have a patient with severe Morgellons- I didn't want to think about this). I added low dose Cipro and gave her a couple doses of Ivermectin. These weird things improved. I switched gears and put her on Minocin. We were 7 months in. The cortef had been a success and was stopped. A strange pruritic rash improved with antihistamines. A stool test for gluten sensitivity was suggested. She couldn't afford it, so she tried an empirical gluten free diet. Colitis symptoms improved. The original symptoms were about 50% better. 9 months in her antibiotics were ramped up again: Amoxil 3gm per day and Zithromax 500mg per day. It worked. She made steady progress. Plaquenil and Questran were used as well. Vitamin D was avoided and Benicar was added to balance out high levels of vit D dihydroxy 1,25. This helped as well. About 15 months in she was 85% better. I did elicit a history of sweats. I reviewed her chart and realized she had not been treated for Babesia. Two months into Zithro, Mepron, Tidamax (which she tolerates well) and Atemensisn she is 95% better. Admittedly I did some things along the way which I might be hesitant to try now. We were able to get past C. diff and plug away. Her colitis is in remission. Her memory and cognition are normal. Her pain is gone. She exercises and functions normally. She is a new person. We are not quite done yet. It is looking good.
I was going through my experimental "CAM" phase. I even tried the vit C and Na protocol. It may have helped a "smidgen." Three months later I bit the bullet. Ramping up the probiotics she started Zithromax and Rifampin. No diarrhea. A herx: fatigue, increased numbness and now orthostatic dizziness. Adrenal insufficiency? I started low dose cortef, 5mg twice daily. Her insurance wouldn't cover Zithro and we switched to Biaxin. Now 5 months into treatment things were gradually improving. She had crawling sensations- saw worms in her stool and had small fibers extruding from her skin.(I have a patient with severe Morgellons- I didn't want to think about this). I added low dose Cipro and gave her a couple doses of Ivermectin. These weird things improved. I switched gears and put her on Minocin. We were 7 months in. The cortef had been a success and was stopped. A strange pruritic rash improved with antihistamines. A stool test for gluten sensitivity was suggested. She couldn't afford it, so she tried an empirical gluten free diet. Colitis symptoms improved. The original symptoms were about 50% better. 9 months in her antibiotics were ramped up again: Amoxil 3gm per day and Zithromax 500mg per day. It worked. She made steady progress. Plaquenil and Questran were used as well. Vitamin D was avoided and Benicar was added to balance out high levels of vit D dihydroxy 1,25. This helped as well. About 15 months in she was 85% better. I did elicit a history of sweats. I reviewed her chart and realized she had not been treated for Babesia. Two months into Zithro, Mepron, Tidamax (which she tolerates well) and Atemensisn she is 95% better. Admittedly I did some things along the way which I might be hesitant to try now. We were able to get past C. diff and plug away. Her colitis is in remission. Her memory and cognition are normal. Her pain is gone. She exercises and functions normally. She is a new person. We are not quite done yet. It is looking good.
Monday, November 17, 2008
Three Legged Monster
I have been treating this critically ill 45 year old man for 2 1/2 months. He had previously been treated by ID specialists with 21 days of Doxycycine. He had been critically ill for 18 months with a rapid downhill spiraling course. He had 3 spinal taps, (I would have said no thank you after the first). Two were negative. The third time he was diagnosed with viral meningitis. He was given a second course of Doxy- thank you. His body is racked with pain. He has unremitting shooting pains and burning of his entire body. Every joint and muscle hurts. His body is weak and he is unable to function. His cognitive deficits have progressed to the point of global dementia. He has restless legs, fevers and chills and soaking sweats. I started him on oral anti Bb meds. He herxed severely. A break in therapy was needed. Low dose malarone was added and his chills and fevers became unbearable. This was put on hold. Despite my concerns, the family was desperate for a more aggressive approach. I was leery, but agreed to give it a try. One month in I started Rocephin. The neuro and musculoskeletal Herx was severe. The decision was made to tough it out. Mepron was added. The Herx was worse: the patient developed a delirium. This abated with a lowering of narcotic analgesics and a reduction in dose of Rocephin. When the Rocephin was ramped up again the Herx returned and was intolerable.The dose of Rocephin was lowered once more and his symptoms settled down. His mental status was at least back to baseline. The soaking sweats of the Babesia Herx persisted. The Mepron was stopped. Malarone one tablet daily was re instituted. The sweats and chills abated. Two legs of the monster were at least being held at bay: Borrelia and Babesia. His blood smear is swarming with the mystery bacteria. It was a stalemate, The patient was circling the tarmac. His pain was minimally improved. His mentation was stable. The drenching sweats were gone. He was also encouraged that the restless leg syndrome had quieted down with Mirapex. His wife was certainly grateful since he had belted her in the face during sleep. I know the Lyme and Babesia were only being tamped down. Every time I upped the ante things got worse. Is it better to treat only one thing at a time as is oft stated? That approach so far had failed. Perhaps it is better to hack away at all three legs at once. Today I set out a trap for the third leg of this dreadful monster. I don't know what the mystery germ is, nonetheless, I cautiously added Zithromax and Rifampin in an effort to throw it off balance. Hopefully the monster will fall. I know if it does I will have to return to the work of chopping away at the other legs.
Sunday, November 16, 2008
Page turner
I should be asleep. But I bolted out of bed, restless, driven and obsessed. How did I end up in the middle of this maelstrom, and where is it headed? I did not choose this disease: It chose me. The story unfolds. A drama. A Robin Cook novel. Only this time it is real. The patients are real. Their illnesses are very real. Dr. K from Clongen calls me and says: "D These are the sickest patients I have ever seen. They look barely alive." I know. One has spirochetes swimming in plain view on a slide made of his blood. Others have blood swarming with mysterious bacteria. Most are young people struck down in the prime of life. They fumble for words which do not come. Their thoughts are scattered and lost in the fog. They get confused and disoriented. Their muscles are weakened and no longer support their weight. Their bodies are consumed with pain. Mysterious shooting pains. Muscle pains. Joint pains. Strange sensations, numbness and tingling and loss of sensation and balance afflict them. Strange fevers and drenching sweats punctuate fragments of disordered sleep. Unbearable headaches without relief. A slow, creeping, silent plague wanders the earth. The silence is deafening. Medical journals flow to my office daily. Nothing. The same list of banal illnesses and therapies is paraded out week after week. There is no mention of this strange and mysterious plague which is eating away at the fabric of so many lives.
Like all good novels, this story has a beginning, a middle and an end. Where do we stand? First chapter I suspect. It has all the trimmings of a medical thriller. There is a deep mystery. A terrible disease is disabling and killing people in plain sight and yet no one seems to notice (or care?). Just like in a Robin Cook novel, unexpected and unassuming protagonists emerge unwittingly, swept up in a drama which they did not seek. And despite this, these unlikely protagonists are compelled to see this thing out. Politics and egos obscure a search for truth. There is a foreboding sense of a deeper conspiracy. Danger signs are everywhere. Yet the protagonists trudge through the mine field laden terrain. The plot unfolds daily in unexpected ways. We turn the pages of this crazy novel, caught up in a world of swirling spirochetes, blood parasites, mysterious bacteria and a spreading dreadful plague. A nail biter. A page turner. Yet unlike a Robin Cook novel, this one is real. Hang in there: we are still in chapter one.
Like all good novels, this story has a beginning, a middle and an end. Where do we stand? First chapter I suspect. It has all the trimmings of a medical thriller. There is a deep mystery. A terrible disease is disabling and killing people in plain sight and yet no one seems to notice (or care?). Just like in a Robin Cook novel, unexpected and unassuming protagonists emerge unwittingly, swept up in a drama which they did not seek. And despite this, these unlikely protagonists are compelled to see this thing out. Politics and egos obscure a search for truth. There is a foreboding sense of a deeper conspiracy. Danger signs are everywhere. Yet the protagonists trudge through the mine field laden terrain. The plot unfolds daily in unexpected ways. We turn the pages of this crazy novel, caught up in a world of swirling spirochetes, blood parasites, mysterious bacteria and a spreading dreadful plague. A nail biter. A page turner. Yet unlike a Robin Cook novel, this one is real. Hang in there: we are still in chapter one.
Thursday, November 13, 2008
Bartonella- Babesia- Bugs- Testing
Clongen has a species PCR runnning for Babesia. It includes 15 species. This is the first test of its kind available. It still won't cover untyped strains. PCR methods are not fool proof.
Here is some evidence for Bartonella proponents. I got back a positive Bartonella species PCR with a negative Bartonella henselae PCR. This suggests that atypical strains of Bartonella in TBD patients do in fact exist. Side bar: On the meds that are supposed to work for atypical Bartonella- Levaquin and Rifampin, she is getting worse. Now that I know what this patient has, I will have to figure out what actually works for this non-typed Bartonella species.
Lyme disease patients have small highly motile gram negative bacteria in their blood. These bacteria are coccobacilli and appear uniform in morphology. They do not adhere to red blood cells. The are present in patients treated with Rocephin, Zithromax and Doxycycline. The DNA sequencing should be done next week. I think they may be GI anerobes from the tick gut. But that is just a wild guess.
Finding out what this bug is may represent a new turn our understanding of this complex poly-microbial disease, and hopefully will offer a new direction regarding possible therapy.
Dr. Kilani mentioned that many physicians are spending a tremendous amount of money ordering tests which are rarely helpful. Here is a suggestion of cost effective screening for patients: Lyme WB. Babesia species PCR. Bartonella species PCR. Ribosomal DNA 16S sequencing for other bacteria. The Bartonella test is optional since it may show up with the RDNA 16S screen. He does not do serology. I would add antibody studies for Ehrlichia and Anaplasma if available. PCR testing for Lyme is rarely positive and should not be done routinely. Other basic information including CBC,Chems,Sed rate, CRP, vit D 25 and 1,25, and B12/folate are essential in my experience. CD57, C3a, C4a: I like to get them out of habit. I have not found that they alter my clinical judgement regarding diagnosis or therapy.
Here is some evidence for Bartonella proponents. I got back a positive Bartonella species PCR with a negative Bartonella henselae PCR. This suggests that atypical strains of Bartonella in TBD patients do in fact exist. Side bar: On the meds that are supposed to work for atypical Bartonella- Levaquin and Rifampin, she is getting worse. Now that I know what this patient has, I will have to figure out what actually works for this non-typed Bartonella species.
Lyme disease patients have small highly motile gram negative bacteria in their blood. These bacteria are coccobacilli and appear uniform in morphology. They do not adhere to red blood cells. The are present in patients treated with Rocephin, Zithromax and Doxycycline. The DNA sequencing should be done next week. I think they may be GI anerobes from the tick gut. But that is just a wild guess.
Finding out what this bug is may represent a new turn our understanding of this complex poly-microbial disease, and hopefully will offer a new direction regarding possible therapy.
Dr. Kilani mentioned that many physicians are spending a tremendous amount of money ordering tests which are rarely helpful. Here is a suggestion of cost effective screening for patients: Lyme WB. Babesia species PCR. Bartonella species PCR. Ribosomal DNA 16S sequencing for other bacteria. The Bartonella test is optional since it may show up with the RDNA 16S screen. He does not do serology. I would add antibody studies for Ehrlichia and Anaplasma if available. PCR testing for Lyme is rarely positive and should not be done routinely. Other basic information including CBC,Chems,Sed rate, CRP, vit D 25 and 1,25, and B12/folate are essential in my experience. CD57, C3a, C4a: I like to get them out of habit. I have not found that they alter my clinical judgement regarding diagnosis or therapy.
Monday, November 10, 2008
Book
A patient brought me another Lyme book to look at. This one was written by a well known LLMD. It gives me pause. I am an allopathic doctor. Rather than defining what I am, this appelation says what I am not. I am not: an osteopath, an herbalist, a practioner of homeopathy or a doctor who specializes in CAM (complementary and alternative medicine). I follow mainstream medical paradigms. I treat diabetes with Glucophage, not dandelion roots. I generally work within a box of evidence based therapies and standard guidelines. As is the case with other allopathic physicians, I am afforded some lattitude to occasionally color outside the lines. It's OK to recommend Saw Palmetto for prostatism or St. John's Wort for depression. Now I treat chronic Lyme disease. It is a new world. I use principals of allopathic medicine, but I use them to treat an illness which itself exists outside the box. The ILADS box is ignored by "real" doctors for the time being. The ILADS guidelines look quite familiar to allopathic physcians. They are written in standard doctor speak.
Lyme treating physicians have a bit of an identity crisis. It seems most approach the disease through the lens of alternative, non-allopathic medicine. This is melded with a smattering of allopathic medicine. This leads to the confusion. Allopathic medicine and complementary, alternative medicine are two separate, distinct disciplines. I see chronic Lyme disease as a devastating epidemic of epic proportion. Based on the premises inherent to my underpinnings as a physician, I have an imperative to treat the illness based on the best scientific evidence utilizing reliable tools which have been effective for other illnesses.
Briefly, here is the story of a woman I saw today. She is in her mid 40s and obese. She came to my office three months ago. She was sent by other family members who had suffered with Lyme disease. She had been sick for more than a year. She had drenching sweats, foot pain,joint pain, body aches and flu like symptoms, brain fog and memory loss, numbness and tingling, impaired balance, urinary symptoms and profound fatigue.
Her labs were CDC positive for Lyme. Her B12 and folate levels were low. I prescribed Ceftin and Minocin and asked her to return in 3 weeks. She misunderstood me. Instead she returned in three months. Surprisingly, all of her symptoms had improved, including the sweats and the cognitive deficits. The standard paradigm would have suggested that she be treated for Babesia and ?Bartonella. Self proclaimed "Lyme doctors" who treat such patients would suggest that she could not improve without a plethora of alternative therapies, including: vitamins, supplements, life style changes, diet and exercise. In truth she ate poorly, did not take supplements and did not exercise. Despite this she improved rapidly.
The task before us- that is the task of understanding and treating Lyme disease is daunting. We are general physicians. At once we must understand the complexities of immunology, microbiology and pharmacology. We are at odds with experts who have forgotten more about these disciplines than we can ever hope to know. Immunologist can spend 5 or more years exploring this ever changing discipline and admit they are only scratching the surface. When iconoclasts, such as those of us who treat chronic Lyme disease, take on the establishment, we better make sure we are right.
I suggest: Avoid terms like LLMD and LAMP. Instead we should indicate that we are ILADS practitioners or IDSA practitioners. We should then indicate whether we are allopathic or alternative practitioners.
Patients need to know their options and understand the biases of their physician.
This book is full of useful and intriguing information and ideas. I am sorry to report that its author got some of the basics wrong.
I think it is improper to suggest that Lyme is transmitted by fleas, flies, gnats, mites and mosquitoes. Lyme is an aerobic bacteria, not anerobic, although it may live under microaeophilic conditions. This is not a trivial point. It determines which anti-microbials will be effective. Penicillins and Cephalosporins, just like Tetracycalines and Macrolides all penetrate mammalian cells. It is incorrect to claim that only the later two classes of antibiotics penetrate within cells. What is correct is that the first two classes of antibiotics may be ineffective against intracellular Borrelia organisms which become L-forms and shed their cell wall.
The immune system is extremely complex. This must be acknowledged when one entertains a discussion of its functions. Bacterial antigens are indeed processed by Macrophages and then presented to lymphocytes. Helper T cells (lymphocytes) facilitate the production of antibodies by B lymphocytes. These B lymphocytes can transform into plasma cells which become antibody factories. There are hundreds of cytokines which are involved in the function of the immune system. The Th1 and Th2 balance of helper T cell lymphocytes is an important part of immune function. Th1 activation is associated with inflammatory cytokines, but it also associated with the elaboration of endogenous peptides which assist in the killing of intracelluar pathogens, such as L-forms of Lyme. Immune cells do have endorphin receptors as mentioned. They also have vitamin D receptors(VDRs). Measurements of dihydroxy 1,25 vitamin D are in fact accurate. This form of vitamin D is the metabolically active form. Vitamin D OH 25 is metabolically inactive. Vitamin D dysregulation with increased active vitamin D does in fact cause a tilt towards the Th1 response away from the Th2 response. This is thought to be a mechanism by which intracellular L forms ensure their survival.
In my experience SPECT scans and MRI scans are very useful. A lumbar puncture does not support the diagnosis of multiple sclerosis as stated. I do not find this procedure to be helpful except in rare cases.
The CD57 test has not proved to be helpful in determining when antibiotics can be stopped. Many factors, including stress and cytokines affect the up and down regulation of this parameter(a subset of natural killer T cells).
There are in fact no "Lyme experts." Recommendations to administer Rocephin in 3 day boluses stem from the conjecture of one well known LLMD. The only evidence based medicine related to the use of Rocephin comes from the work of Brian Fallon at Columbia University. In his studies Rocephin was used continuously.
The IgeneX FISH test for Babesia does not test for multiple species as stated. It only tests for B. microti. A new PCR test in development by Clongen Labs will detect DNA found in 15 well categorized species of Babesia.
It is a stretch to suggest that TSH levels over 2.0 reflect low thyroid function. The consensus amongst physicians is that TSH levels up to approximately 4.5 are normal.
According to my allopathic bias, there is no basis, scientific or otherwise, to support the use of the many herbal therapies, alternative therapies or the value of the anti-inflammatory diet discussed.
My concern is that a focus on taking 15 herbs and vitamin supplements may detract from efforts to treat a serious infectious disease with hard hitting antibiotics.
Again, as I hope I have made clear: this is my bias. I ask other physicians to make clear from the start what biases they have.
I laud all doctors who are willing to take on an establishment which for whatever reasons, seems determined to fight our efforts to help our patients. I cannot say that CAM is ineffective. I can say that I personally have treated many patients who had previously received extensive CAM therapy without benefits. Many of these patients have responded very well to vigorous allopathic therapies.
Lyme treating physicians have a bit of an identity crisis. It seems most approach the disease through the lens of alternative, non-allopathic medicine. This is melded with a smattering of allopathic medicine. This leads to the confusion. Allopathic medicine and complementary, alternative medicine are two separate, distinct disciplines. I see chronic Lyme disease as a devastating epidemic of epic proportion. Based on the premises inherent to my underpinnings as a physician, I have an imperative to treat the illness based on the best scientific evidence utilizing reliable tools which have been effective for other illnesses.
Briefly, here is the story of a woman I saw today. She is in her mid 40s and obese. She came to my office three months ago. She was sent by other family members who had suffered with Lyme disease. She had been sick for more than a year. She had drenching sweats, foot pain,joint pain, body aches and flu like symptoms, brain fog and memory loss, numbness and tingling, impaired balance, urinary symptoms and profound fatigue.
Her labs were CDC positive for Lyme. Her B12 and folate levels were low. I prescribed Ceftin and Minocin and asked her to return in 3 weeks. She misunderstood me. Instead she returned in three months. Surprisingly, all of her symptoms had improved, including the sweats and the cognitive deficits. The standard paradigm would have suggested that she be treated for Babesia and ?Bartonella. Self proclaimed "Lyme doctors" who treat such patients would suggest that she could not improve without a plethora of alternative therapies, including: vitamins, supplements, life style changes, diet and exercise. In truth she ate poorly, did not take supplements and did not exercise. Despite this she improved rapidly.
The task before us- that is the task of understanding and treating Lyme disease is daunting. We are general physicians. At once we must understand the complexities of immunology, microbiology and pharmacology. We are at odds with experts who have forgotten more about these disciplines than we can ever hope to know. Immunologist can spend 5 or more years exploring this ever changing discipline and admit they are only scratching the surface. When iconoclasts, such as those of us who treat chronic Lyme disease, take on the establishment, we better make sure we are right.
I suggest: Avoid terms like LLMD and LAMP. Instead we should indicate that we are ILADS practitioners or IDSA practitioners. We should then indicate whether we are allopathic or alternative practitioners.
Patients need to know their options and understand the biases of their physician.
This book is full of useful and intriguing information and ideas. I am sorry to report that its author got some of the basics wrong.
I think it is improper to suggest that Lyme is transmitted by fleas, flies, gnats, mites and mosquitoes. Lyme is an aerobic bacteria, not anerobic, although it may live under microaeophilic conditions. This is not a trivial point. It determines which anti-microbials will be effective. Penicillins and Cephalosporins, just like Tetracycalines and Macrolides all penetrate mammalian cells. It is incorrect to claim that only the later two classes of antibiotics penetrate within cells. What is correct is that the first two classes of antibiotics may be ineffective against intracellular Borrelia organisms which become L-forms and shed their cell wall.
The immune system is extremely complex. This must be acknowledged when one entertains a discussion of its functions. Bacterial antigens are indeed processed by Macrophages and then presented to lymphocytes. Helper T cells (lymphocytes) facilitate the production of antibodies by B lymphocytes. These B lymphocytes can transform into plasma cells which become antibody factories. There are hundreds of cytokines which are involved in the function of the immune system. The Th1 and Th2 balance of helper T cell lymphocytes is an important part of immune function. Th1 activation is associated with inflammatory cytokines, but it also associated with the elaboration of endogenous peptides which assist in the killing of intracelluar pathogens, such as L-forms of Lyme. Immune cells do have endorphin receptors as mentioned. They also have vitamin D receptors(VDRs). Measurements of dihydroxy 1,25 vitamin D are in fact accurate. This form of vitamin D is the metabolically active form. Vitamin D OH 25 is metabolically inactive. Vitamin D dysregulation with increased active vitamin D does in fact cause a tilt towards the Th1 response away from the Th2 response. This is thought to be a mechanism by which intracellular L forms ensure their survival.
In my experience SPECT scans and MRI scans are very useful. A lumbar puncture does not support the diagnosis of multiple sclerosis as stated. I do not find this procedure to be helpful except in rare cases.
The CD57 test has not proved to be helpful in determining when antibiotics can be stopped. Many factors, including stress and cytokines affect the up and down regulation of this parameter(a subset of natural killer T cells).
There are in fact no "Lyme experts." Recommendations to administer Rocephin in 3 day boluses stem from the conjecture of one well known LLMD. The only evidence based medicine related to the use of Rocephin comes from the work of Brian Fallon at Columbia University. In his studies Rocephin was used continuously.
The IgeneX FISH test for Babesia does not test for multiple species as stated. It only tests for B. microti. A new PCR test in development by Clongen Labs will detect DNA found in 15 well categorized species of Babesia.
It is a stretch to suggest that TSH levels over 2.0 reflect low thyroid function. The consensus amongst physicians is that TSH levels up to approximately 4.5 are normal.
According to my allopathic bias, there is no basis, scientific or otherwise, to support the use of the many herbal therapies, alternative therapies or the value of the anti-inflammatory diet discussed.
My concern is that a focus on taking 15 herbs and vitamin supplements may detract from efforts to treat a serious infectious disease with hard hitting antibiotics.
Again, as I hope I have made clear: this is my bias. I ask other physicians to make clear from the start what biases they have.
I laud all doctors who are willing to take on an establishment which for whatever reasons, seems determined to fight our efforts to help our patients. I cannot say that CAM is ineffective. I can say that I personally have treated many patients who had previously received extensive CAM therapy without benefits. Many of these patients have responded very well to vigorous allopathic therapies.
Fibromyalgia
Here is a case of a woman in her mid fifties. She was diagnosed with severe fibromyalgia. I have been taking care of her for 15 years. By 2002 she was opioid dependent and on her way to total disability. She was treated symptomatically with the usual fare: opiates, Prozac, Ritalin, NSAIDs, Klonopin and T3 (thyroid) supplemention. She began a long therapy with recurrent trigger point injections which afforded her some relief. Along the way drugs like Lyrica were added. Nothing helped all that much. In addition to incapacitating pain and myofascial muscle pain she develped progressive cognitive impairments which tied into her longstanding fatigue. Finally in June 2006 I suggested she try Doxycyline. Her screeenings for Lyme and TBD had been negative. There was no improvement. She was not sold on the ideas and stopped the antibiotics after a couple of months. With progressive memory loss she agreed to try Ceftin and Zithromax. She got nausea and vomiting for her troubles and increased pain. She was not convinced but agreed to humor me. I tried Ketek. Repeat Lyme and TBD antibodies remained negative. There was some noticeable improvement. Her antibiotics were switched up to Cipro, Doxycyline and Flagyl. She was seen two months later. She developed mouth sores and had stopped the antibiotics on her own. The fatigue, pain and other symptoms had improved but were now worse. Ceftin was reintroduced. She was feeling better the next month but complained of GI intolerance to the Ceftin. Minocin was substituted. Two months later she was worse. She was placed on Amoxil, Biaxin and Plaquenil.No benefit. The antibiotics all seemed to have difficult side effects and she wasn't convinced that they were helping. She went on and off antibiotics trying different combinations. Several months later a cocktail of Amoxil, Flagyl and Cipro seemed to be helping. The pain was getting much better. The fatigue persisted. She stayed the course through good and bad months. IgeneX testing was negative with some critical IND bands. A course of Levaquin- felt worse. Then back to Amoxil,Biaxin and Flagyl. Over several months the dose of Amoxil was ramped up from 2 to 3 grams per day. And then something unexpected and dramatic occurred. She came into my office recently and reported that she was better, much better. The pain, fatigue and cognitive issues were dramatically improved. We started the process of hopefully weaning her off a plethora of medications, most of which had not been terribly effective.
Fibromyalgia; Chronic fatigue syndrome; Depression; Chronic opioid dependence; all with a sense of unmitigating suffering, intertwined with months of hopeless desperation. Twenty years of mind boggling pain- phsyical and psycological dysfunction with no relief in sight. How many of us could have hung in there this long? She had been written off by her past physicians because they did not listen. She hung in there with me. First, I was a sympathetic doctor who listened, believed in her, and did my best to alleviate her suffering. Sadly, this was something novel to a patient who had thoroughly experienced the machinery of American medicine. Then she returned the favor. As I slowly became a convert to a new way of thinking she listened to me. She was skeptical of all the things I said. Still, she believed in me, and went along for the ride. We are both cautiously opptomistic. What will next month's visit bring? Hopefully more good news!
So what have I been treating her for? Theortically Lyme disease. Or was it some other chronic bacterial infection like Mycoplasma or CPN, or something as of yet undiscovered. Proof? There is none. Sure there were/are abnormal neurological signs such as decreased sensation and a positive Babinsky, so what? There are mild laboratory abnormalities like a high C3a level. Mostly the improvements are subjective. There is less pain and less myofascial tenderness; she feels better and says she can think more clearly without stumbling over her words.
As physicians we have to be humble and admit that sometimes we are not really sure what we are treating. Mainstream doctors who are quick to debunk such theories and therapies, offer no alternative methods to help such long suffering patients.
So those of us in the trenches will keep searching for answers as we do our best for our patients.
Fibromyalgia; Chronic fatigue syndrome; Depression; Chronic opioid dependence; all with a sense of unmitigating suffering, intertwined with months of hopeless desperation. Twenty years of mind boggling pain- phsyical and psycological dysfunction with no relief in sight. How many of us could have hung in there this long? She had been written off by her past physicians because they did not listen. She hung in there with me. First, I was a sympathetic doctor who listened, believed in her, and did my best to alleviate her suffering. Sadly, this was something novel to a patient who had thoroughly experienced the machinery of American medicine. Then she returned the favor. As I slowly became a convert to a new way of thinking she listened to me. She was skeptical of all the things I said. Still, she believed in me, and went along for the ride. We are both cautiously opptomistic. What will next month's visit bring? Hopefully more good news!
So what have I been treating her for? Theortically Lyme disease. Or was it some other chronic bacterial infection like Mycoplasma or CPN, or something as of yet undiscovered. Proof? There is none. Sure there were/are abnormal neurological signs such as decreased sensation and a positive Babinsky, so what? There are mild laboratory abnormalities like a high C3a level. Mostly the improvements are subjective. There is less pain and less myofascial tenderness; she feels better and says she can think more clearly without stumbling over her words.
As physicians we have to be humble and admit that sometimes we are not really sure what we are treating. Mainstream doctors who are quick to debunk such theories and therapies, offer no alternative methods to help such long suffering patients.
So those of us in the trenches will keep searching for answers as we do our best for our patients.
Bartonella Yes! or Not
A longstanding patient, a woman in her mid 40s complained of new onset arthritis about 3 years ago. My standard work up for ReA (reactive arhtritis) included antibody testing for Salmonella species. In previous blogs I have noted that chronic Lyme syndrome resembles ReA as described in Harrison's textbook of medicine. At that time I performed a standard Lyme WB which as negative. I will again note that Harrison's indicated that treatment for the putative infection did not alter the course of the arthritis. At that time I was looking at the work of several other physicians. Dr, Gabe Mirkin, a local radio personality and iconoclastic physician had been recommending the use of antibiotics for arthritis and other chronic illnesses like fibromyalgia. He reported that he "cured" his wife's rheumatoid arthritis with antibiotics.He strongly harped about the infectious disease connection to chronic illness and was censured by is colleagues who considered him an eccentric "nut." Be believed that chronic Myoplasma and Chlamydia infections were the cause. I thought there might be some validity to his claims. You don't hear much about Mirkin. I think he was ahead of time. But like the parable of the 3 blind men, he was feeling a different part of the elephant. Literature widely available in rheumatology texts, for many years, has consistently demonstrated that tetracycalines were effective for rheurmatoid arthritis. For some reason, rheumatologists have ignored this data. It upset their paradigm. They believed it worked via an anti-inflammatory effect, not antimicrobial. In fact, this is an argument which is still marshaled against the use of antibiotics for chronic "rheumatological" disorders. I am troubled by the logic that Methotrexate and Enbrel, which may cause immunosuppresion and cancer, are safer than long term antibiotics. I tried her on a course of Levaquin which improved her symptoms. It was taken for only two months. The patient seem to go into remission.
Six months later she returned with a collection of different symptoms. These included: fatigue, recurrent joint pain, numbness and tingling, blurred vision and forgetfulness. A Lyme work up was initiated and she was started on Doxycycline.
Her labs showed low vit D OH 25 (8) and Lyme WB now positive on 10 band IgG in the
18, 28 and 41 positions. Two weeks later Ceftin was added. One month later she complained of arm weakness, fatigue, tingling and numbness blurred vision. Her memory was better. She had generalized malaise and was concerned that the abtibiotics were causing side effects. She was changed to Amoxil and Biaxin as well as Plaquenil, and a five day course of Flagyl. One month later nearly all her initial symptoms were better. She did have continued burning sensations and noted heel pain. Her fatigue and cognitive issues were better. Three months later symptoms were fluctuant but headed in the right direction. A yeast infection was treated.
Urinary symptoms were present. She was treated with a course of Cipro and antibiotics were stopped. She felt well. Four months later symptoms returned. These included: palpitations, shortness of breath, fatigue, heel pain. All prior cognitive issues were resolved and had not returned. She was placed on Biaxin and Plaquenil.
Two months later she was worse. Some forgetfulness had returned. Amoxil and Flagyl were reintroduced. She stopped the antibiotics after a month and felt well. Six months later symptoms recurred. She had burning sensations, a sensation of cold feet and hot flashes. There was no pain, fatigue, cognitive dysfunction or weakness.
More lab studies were done. The FSH revealed that she was not post menopausal. Other studies from Labcorp showed that her vitamin D ratio was reversed with high 1,25 levels. Her Lyme C6 peptide had increased from 0.16 to 0.54. B12 and folate were normal. Her Bartonella serolgoy was interesting. Bartonella henselae IgG 1:640 positive, B. quintana IgG 1:1280 very positive. She was started on Levaquin and will receive follow up.
The patient's course perhaps demonstrates the persistence of Bartonella. It certainly demonstrates my evolution as a LLMD. This patient is unusual in that she took repeated courses of antibiotics which she stopped on her own, experiencing remissions and relapses. Each relapse improved with relatively short courses of antibiotics.She had prior serological tests for Babesia which were negative but this was the first time I had tested her for Bartonella. She had avoided much lab work due to cost and had largely been treated empirically.
Bartonella is real. It may be associated with tick borne disease. In Harrison's text it is associated with: cat scratch disease (which can have life threatening complications), Trench fever, endocarditis and other rare but serious disorders. Recommended theapy includes: Zithromax, Doxycyline, Rocephin and gentamycin for endocarditis. Bartonella bacilliformis is an acute, serious illness. It seems to be limited to Peru. Bacillary angiomatosis, caused by By B. henselae and B. quintana is seen primarily in AIDS patients. It is associated with cutaneous lesions and a life threatening multi-system disorder. Interestingly, the 16S DNA sequencing test is the gold standard. Serology is thought to be unreliable. Specifically, Harrison's states that Bactrim, Penicillins, Cephalosporins and CIPRO were not effective.
This begs the question(s): Is Bartonella a significant tick borne infection? What are Baronella like organisms? Why do LLMDS claim they are in the Bartonella genus?
Why do some patients respond to quinolones when other drugs fail? Did I do the right thing, prescribing Levaquin for this patient? Does she have real ongoing infection with Bartonella or do these IgG antibodies represent inactive, curred disease?
Should I insist she have a 16S sequencing of any bacteria which may show up in her blood? Do Bartonella species in fact behave differently in patients with tick borne illness or our we on the wrong path? I would like to know the answers.
As a side bar: What are those coccobacillary organisms that keep showing up in the blood of my patients. It doesn't appear to be particularly pathogenic. Sepsis (blood) infection, with pathogenic bacteria is very serious indeed with traditional organisms such as Strep, E.coli and many others. Bacteremia occurs with brushing our teeth. It should be very transient. Hundreds of dental bacteria remain unidentified.
Are we tilting at wind mills? Are we in fact trying to nail Jello to the wall as claimed by our detractors? One doctor says something. Another agrees. The flock jumps on board. Is this any different than what IDSA doctors do? We can do better.
Six months later she returned with a collection of different symptoms. These included: fatigue, recurrent joint pain, numbness and tingling, blurred vision and forgetfulness. A Lyme work up was initiated and she was started on Doxycycline.
Her labs showed low vit D OH 25 (8) and Lyme WB now positive on 10 band IgG in the
18, 28 and 41 positions. Two weeks later Ceftin was added. One month later she complained of arm weakness, fatigue, tingling and numbness blurred vision. Her memory was better. She had generalized malaise and was concerned that the abtibiotics were causing side effects. She was changed to Amoxil and Biaxin as well as Plaquenil, and a five day course of Flagyl. One month later nearly all her initial symptoms were better. She did have continued burning sensations and noted heel pain. Her fatigue and cognitive issues were better. Three months later symptoms were fluctuant but headed in the right direction. A yeast infection was treated.
Urinary symptoms were present. She was treated with a course of Cipro and antibiotics were stopped. She felt well. Four months later symptoms returned. These included: palpitations, shortness of breath, fatigue, heel pain. All prior cognitive issues were resolved and had not returned. She was placed on Biaxin and Plaquenil.
Two months later she was worse. Some forgetfulness had returned. Amoxil and Flagyl were reintroduced. She stopped the antibiotics after a month and felt well. Six months later symptoms recurred. She had burning sensations, a sensation of cold feet and hot flashes. There was no pain, fatigue, cognitive dysfunction or weakness.
More lab studies were done. The FSH revealed that she was not post menopausal. Other studies from Labcorp showed that her vitamin D ratio was reversed with high 1,25 levels. Her Lyme C6 peptide had increased from 0.16 to 0.54. B12 and folate were normal. Her Bartonella serolgoy was interesting. Bartonella henselae IgG 1:640 positive, B. quintana IgG 1:1280 very positive. She was started on Levaquin and will receive follow up.
The patient's course perhaps demonstrates the persistence of Bartonella. It certainly demonstrates my evolution as a LLMD. This patient is unusual in that she took repeated courses of antibiotics which she stopped on her own, experiencing remissions and relapses. Each relapse improved with relatively short courses of antibiotics.She had prior serological tests for Babesia which were negative but this was the first time I had tested her for Bartonella. She had avoided much lab work due to cost and had largely been treated empirically.
Bartonella is real. It may be associated with tick borne disease. In Harrison's text it is associated with: cat scratch disease (which can have life threatening complications), Trench fever, endocarditis and other rare but serious disorders. Recommended theapy includes: Zithromax, Doxycyline, Rocephin and gentamycin for endocarditis. Bartonella bacilliformis is an acute, serious illness. It seems to be limited to Peru. Bacillary angiomatosis, caused by By B. henselae and B. quintana is seen primarily in AIDS patients. It is associated with cutaneous lesions and a life threatening multi-system disorder. Interestingly, the 16S DNA sequencing test is the gold standard. Serology is thought to be unreliable. Specifically, Harrison's states that Bactrim, Penicillins, Cephalosporins and CIPRO were not effective.
This begs the question(s): Is Bartonella a significant tick borne infection? What are Baronella like organisms? Why do LLMDS claim they are in the Bartonella genus?
Why do some patients respond to quinolones when other drugs fail? Did I do the right thing, prescribing Levaquin for this patient? Does she have real ongoing infection with Bartonella or do these IgG antibodies represent inactive, curred disease?
Should I insist she have a 16S sequencing of any bacteria which may show up in her blood? Do Bartonella species in fact behave differently in patients with tick borne illness or our we on the wrong path? I would like to know the answers.
As a side bar: What are those coccobacillary organisms that keep showing up in the blood of my patients. It doesn't appear to be particularly pathogenic. Sepsis (blood) infection, with pathogenic bacteria is very serious indeed with traditional organisms such as Strep, E.coli and many others. Bacteremia occurs with brushing our teeth. It should be very transient. Hundreds of dental bacteria remain unidentified.
Are we tilting at wind mills? Are we in fact trying to nail Jello to the wall as claimed by our detractors? One doctor says something. Another agrees. The flock jumps on board. Is this any different than what IDSA doctors do? We can do better.
Friday, November 7, 2008
Patient with positive serology for 4 tick borne infections and surprising presentation
A 50 something year old male patient joined my general family practice about 3 and 1/2 years ago. He was fairly healthy but described an unusual history. Some months before he suffered a rib fracture. His orthopedic surgeon prescribed miacalcin, the hormone calcitonin, to speed up the healing of his fracture. He developed acute psychiatric symptoms. He became depressed and then manic. He was diagnosed with bipolar disease and anxiety precipitated by calcitonin. Over the next two years his psychiatric disorder worsened and he was placed on an increasing number of psychotropic agents by various psychiatrists, who were somewhat miffed by the odd atypical presentation in this man.
A little over one year ago he came to me office complaining of skin discoloration. He had two rashes. One was a classic EM rash on the right thigh.
A little more history. He was an avid deer hunter. He did have some fatigue and neck pain. He did recall a brief, minor episode of fever and chills three months preceding the rash. Besides the psychiatric symptoms he was generally robust and felt quite well.
Blood samples were sent to Quest Diagnostics: The CBC was normal. B12 and folate were normal. His vitamin D levels were normal. Babesia microti- elevated IgM titer. Bartonella Quintant- elevated IgM titer. Anaplasmosis phagoctytophilum- very high IgM titer. Borrelia burdorferi- Western Blot- 9/10 IgG bands and 3/3 IgM bands. Lyme C6 antibody index- over 6.0.
At this point his psychiatrist had him on Depakote- a mood stabilizer 1750mg per day (a very high dose), Seroquel- an anti-psycotic used for severe mania and Klonopin, a tranquilizer used for anxiety and the anti-depressant Lexapro.
He came to my office to review the lab results. He looked remarkably well. I felt like I needed some of his Klonopin to figure out how to treat him.(Humor- if the board is reading this). I stared with Zitromax and Mepron for 3 weeks only. At that point his neck pain was gone. He had no chills or flu like symptoms. He had only mimimal fatigue and nominal joint pains- mostly knees. His mood swings were perhaps a little better. He was treated with a month of Amoxil one gram twice daily and Cipro 500 mg twice daily. No Herx- feeling well. He was treated with Amoxil- same dose and Doxycycline 400 mg per day for 6 weeks. Blood to Labcorp: CD57 120, CBC- WBC count 5.2 (normal) but new right shift. This means there were more lymphocytes and fewer neutrophils than usually seen. The Lyme WB showed IgG bands 10/10, IgM 2/3
bands. Bartonella, Babesia and Ehrlichia were negative. The C6 titer was 5.5. The folic acid level had increased from 18 to greater than 24. He was not taking vitamins. After 12 weeks Flagyl was added. He was now taking Amoxil- same dose, Doxyclycine- same dose and Flagyl 500 mg daily. His energy level was normal. He had not medical symptoms. His psychiatric symptoms were improving quickly and his pychiatrist was quickly weaning him from psychotropic medicines. After an additional 8 weeks his Doxycycline was changed to Biaxin. He had no symptoms related to tick borne illness, except mild anxiety and mood swings.
Six months after his first presentation, still on the same antibiotics, his psychiatrist had stopped Depakote and Seroquel. The dose of Klonopin was in a process of being tapered off. He was still on Lexapro. Two months later he was off Klonopin. His prior antibiotics were discontinued. He was changed to Minocin 100 mg twice daily. Most recent labs: Lyme WB IgG 9/10, IgM 1/3. CBC- no change- persistent right shift, C6 index- 5.2. Routine labs including autoimmune and markers for inflammation are normal.
His "Bipolar" disorder is in remission.
He is convinced it all started with that darn Miacalcin. The PDR states that Miacalcin is synthetic calcitonin, a hormone secreted by the parathyroid glands. It's primary effect is to strenthen bone by inhibiting the activity of osteoclasts, the cells which remove bone matrix. It is rarely reported to cause depression and anxiety: reasons unknown. It has not been linked to bipolar disease. Does it have a feedback effect on vitamin D or cell mediated immune functions? This has not been reported.
The psychiatric symptoms preceeding the acute typical presentation of Lyme and tick borne illness by some years.
I suspect he had chronic Lyme causing an atypical psychiatric disorder with superimposed acute re-infection. Miacalcin? A red herring?
He is in his mid 50s. He is the picture of health. He has no physical or cognitive limitations. He mountain bikes miles. And by the way, he still hunts deer.
A little over one year ago he came to me office complaining of skin discoloration. He had two rashes. One was a classic EM rash on the right thigh.
A little more history. He was an avid deer hunter. He did have some fatigue and neck pain. He did recall a brief, minor episode of fever and chills three months preceding the rash. Besides the psychiatric symptoms he was generally robust and felt quite well.
Blood samples were sent to Quest Diagnostics: The CBC was normal. B12 and folate were normal. His vitamin D levels were normal. Babesia microti- elevated IgM titer. Bartonella Quintant- elevated IgM titer. Anaplasmosis phagoctytophilum- very high IgM titer. Borrelia burdorferi- Western Blot- 9/10 IgG bands and 3/3 IgM bands. Lyme C6 antibody index- over 6.0.
At this point his psychiatrist had him on Depakote- a mood stabilizer 1750mg per day (a very high dose), Seroquel- an anti-psycotic used for severe mania and Klonopin, a tranquilizer used for anxiety and the anti-depressant Lexapro.
He came to my office to review the lab results. He looked remarkably well. I felt like I needed some of his Klonopin to figure out how to treat him.(Humor- if the board is reading this). I stared with Zitromax and Mepron for 3 weeks only. At that point his neck pain was gone. He had no chills or flu like symptoms. He had only mimimal fatigue and nominal joint pains- mostly knees. His mood swings were perhaps a little better. He was treated with a month of Amoxil one gram twice daily and Cipro 500 mg twice daily. No Herx- feeling well. He was treated with Amoxil- same dose and Doxycycline 400 mg per day for 6 weeks. Blood to Labcorp: CD57 120, CBC- WBC count 5.2 (normal) but new right shift. This means there were more lymphocytes and fewer neutrophils than usually seen. The Lyme WB showed IgG bands 10/10, IgM 2/3
bands. Bartonella, Babesia and Ehrlichia were negative. The C6 titer was 5.5. The folic acid level had increased from 18 to greater than 24. He was not taking vitamins. After 12 weeks Flagyl was added. He was now taking Amoxil- same dose, Doxyclycine- same dose and Flagyl 500 mg daily. His energy level was normal. He had not medical symptoms. His psychiatric symptoms were improving quickly and his pychiatrist was quickly weaning him from psychotropic medicines. After an additional 8 weeks his Doxycycline was changed to Biaxin. He had no symptoms related to tick borne illness, except mild anxiety and mood swings.
Six months after his first presentation, still on the same antibiotics, his psychiatrist had stopped Depakote and Seroquel. The dose of Klonopin was in a process of being tapered off. He was still on Lexapro. Two months later he was off Klonopin. His prior antibiotics were discontinued. He was changed to Minocin 100 mg twice daily. Most recent labs: Lyme WB IgG 9/10, IgM 1/3. CBC- no change- persistent right shift, C6 index- 5.2. Routine labs including autoimmune and markers for inflammation are normal.
His "Bipolar" disorder is in remission.
He is convinced it all started with that darn Miacalcin. The PDR states that Miacalcin is synthetic calcitonin, a hormone secreted by the parathyroid glands. It's primary effect is to strenthen bone by inhibiting the activity of osteoclasts, the cells which remove bone matrix. It is rarely reported to cause depression and anxiety: reasons unknown. It has not been linked to bipolar disease. Does it have a feedback effect on vitamin D or cell mediated immune functions? This has not been reported.
The psychiatric symptoms preceeding the acute typical presentation of Lyme and tick borne illness by some years.
I suspect he had chronic Lyme causing an atypical psychiatric disorder with superimposed acute re-infection. Miacalcin? A red herring?
He is in his mid 50s. He is the picture of health. He has no physical or cognitive limitations. He mountain bikes miles. And by the way, he still hunts deer.
Tuesday, November 4, 2008
Pieces of the puzzle
Tough case I have been treated forever. Every symptom in the book. She went to a "famous" LLMD and now she is getting better! He diagnosed Bartonella (clinically): She has already been treated for this in spades. This time she is getting better. RX: Minocin, Zithromax and Rifampin. Is there something special about this combo? It involves two separate protein synthesis inhibitors and an RNA inhibitor. I had used the same stuff and more, not all at the same time. Now she is also using the gluten free diet I recommended (He agreed). What's working?
Does Lyme cause gluten sensitivity or does it just make an underlying gluten issue more problematic? I don't know. The patients don't have celiac disease. But- the tTG IgA level is greater than zero. The antigliadin antibody is greater than zero. The stool antigliadin antibody level is elevated as tested by Enterolab in TX.
The diet frequently makes a surprising difference. It is a difficult diet; it must be strictly adhered to; improvement won't occur for at least 8 weeks.
But I really want to talk about B12 and especially folic acid. The levels can be quite low, especially in sicker patients. The patients do not have pernicious anemia or any obvious GI dysfunction. What are the causes of folate deficiency? Medical texts claim: poor diet, alcoholism, GI maladsorption, drugs like sulfonamides and INH which compete with folate metabolites and "chronic illness." None of these apply. Besides, folic acid levels can remain very low in the face of massive supplementation. Hemolysis is also listed. This is what makes sense to me. Red blood cells may be infected with bacteria like Ehlichia and Bartonella. This in turn leads to an increased turn over of RBCs. Nutrients required in the manufacture of red cells such as B12 and folic acid become "lost?" in the process. The process occurs rather slowly. Overt hemolysis is not observed. If significant hemolysis were to occur then urine dip would show blood (myoglobin) with no RBCs. The serum LDH level, related to lysed RBCs would be elevated. The patient would be anemic. Haptoglobin levels would be increased. The reticulocyte count would be elevated.
I don't see these things (I also don't test for them).
Lots of RBCs with bacteria can be seen on blood smears. Something must be happening to infected RBCs. Babesia should do the same. But Babesia are hard to find on a blood smear. There doesn't seem to be enough organisms to cause the same effect. Perhaps the organisms are infecting progenitor cells in the bone marrow where such effects occur unseen. The idea of bacteria like Borrelia competing for use of these nutrients doesn't make sense. vitamins are trace nutrients needed to complete enzymatic functions. B12 and folate are used for red blood cell synthesis and nervous tissues. Spriochetes and other bacteria do not have these needs. Why would they compete for these nutrients? Lyme- Tick Borne Disease patients frequently have a mix of hematological abnormalities that have not been explained or cataloged: Unexplained anemias, low white cell counts, low neutrophil counts, increased lymphocyte counts, low platelet counts and other abnormalities which seem to vary from patient to patient. If I were to write a book about tick borne disease a whole chapter could be dedicated to hematological abnormalities- if I ever figure them out.
I am rambling a bit, but these is about pieces of the puzzle- see title.
Perhaps things like Bartonella do cause mild flu like symptoms and chills (min-hemolysis?) No. why would cells rupture with synchrony. It should be a slow trickling process. Wait. The same should be true about Babesia. Why then do patients experience drenching sweats and shaking chills. It really isn't like malaria where large numbers of blood parasites can be observed in red cells causing obvious hemolysis. Perhaps it is toxin medicated with a central hypothalamic effect.I have more questions than answers.
I am convinced that B12 and folic acid are key puzzle pieces. Where do they fit?
And where does Bartonella fit and what are the best treatments? Finally, do these two pieces of the puzzle dovetail?
Does Lyme cause gluten sensitivity or does it just make an underlying gluten issue more problematic? I don't know. The patients don't have celiac disease. But- the tTG IgA level is greater than zero. The antigliadin antibody is greater than zero. The stool antigliadin antibody level is elevated as tested by Enterolab in TX.
The diet frequently makes a surprising difference. It is a difficult diet; it must be strictly adhered to; improvement won't occur for at least 8 weeks.
But I really want to talk about B12 and especially folic acid. The levels can be quite low, especially in sicker patients. The patients do not have pernicious anemia or any obvious GI dysfunction. What are the causes of folate deficiency? Medical texts claim: poor diet, alcoholism, GI maladsorption, drugs like sulfonamides and INH which compete with folate metabolites and "chronic illness." None of these apply. Besides, folic acid levels can remain very low in the face of massive supplementation. Hemolysis is also listed. This is what makes sense to me. Red blood cells may be infected with bacteria like Ehlichia and Bartonella. This in turn leads to an increased turn over of RBCs. Nutrients required in the manufacture of red cells such as B12 and folic acid become "lost?" in the process. The process occurs rather slowly. Overt hemolysis is not observed. If significant hemolysis were to occur then urine dip would show blood (myoglobin) with no RBCs. The serum LDH level, related to lysed RBCs would be elevated. The patient would be anemic. Haptoglobin levels would be increased. The reticulocyte count would be elevated.
I don't see these things (I also don't test for them).
Lots of RBCs with bacteria can be seen on blood smears. Something must be happening to infected RBCs. Babesia should do the same. But Babesia are hard to find on a blood smear. There doesn't seem to be enough organisms to cause the same effect. Perhaps the organisms are infecting progenitor cells in the bone marrow where such effects occur unseen. The idea of bacteria like Borrelia competing for use of these nutrients doesn't make sense. vitamins are trace nutrients needed to complete enzymatic functions. B12 and folate are used for red blood cell synthesis and nervous tissues. Spriochetes and other bacteria do not have these needs. Why would they compete for these nutrients? Lyme- Tick Borne Disease patients frequently have a mix of hematological abnormalities that have not been explained or cataloged: Unexplained anemias, low white cell counts, low neutrophil counts, increased lymphocyte counts, low platelet counts and other abnormalities which seem to vary from patient to patient. If I were to write a book about tick borne disease a whole chapter could be dedicated to hematological abnormalities- if I ever figure them out.
I am rambling a bit, but these is about pieces of the puzzle- see title.
Perhaps things like Bartonella do cause mild flu like symptoms and chills (min-hemolysis?) No. why would cells rupture with synchrony. It should be a slow trickling process. Wait. The same should be true about Babesia. Why then do patients experience drenching sweats and shaking chills. It really isn't like malaria where large numbers of blood parasites can be observed in red cells causing obvious hemolysis. Perhaps it is toxin medicated with a central hypothalamic effect.I have more questions than answers.
I am convinced that B12 and folic acid are key puzzle pieces. Where do they fit?
And where does Bartonella fit and what are the best treatments? Finally, do these two pieces of the puzzle dovetail?
Monday, November 3, 2008
Cost effective testing
The first question is whether testing should be done at all. Some might think of Lyme disease as a multi system disorder causing at least moderate disability. Others might think of it as a wide spectrum disorder with symptoms ranging from very mild to severe. In a way it is philosophical question. Many persons suffer with varying manifestations of chronic Lyme infection. Many patients are "colonized" with Lyme spirochetes but not necessarily ill, or very subtly ill. One should not test at all unless treatment is desired based on an assessment of symptoms. Treating patients with minimal symptoms can still be a daunting process. In many such cases watchful waiting may be the best course.
Given that TBD (tick borne disease) is suspected, also called LBC (Lyme Boreliosis complex), (Note these terms are replacing the term chronic Lyme disease because of the increasing assumption of a poly-microbial syndrome), one must give careful consideration regarding the use of ancillary laboratory testing.
The first phase of testing is of course the history and physical exam.
As we move into the realm of lab tests the first priority is to document exposure to Borrelia burdorferi, the Lyme spirochete. Most patients have insurance. This means that tests at "mill labs" like Labcorp and Quest are covered. This is usually the starting place. These labs do a mediocre job with serological(antibody) tests, but appear to do a poor job with PCR testing. Don't order the standard Lyme antibody test. This means an ELISA test will be done. We know this is a poor screening test. Order a direct Lyme Western Blot test. This is a better, yet still poor test. It only reports 13/28 bands. Despite this, sometimes we get lucky. Labcorp and Quest will do serological tests for Ehrlichia, Bartonella and Babesia. Labcorp does a PCR for Anaplasmosis which is poor, while Quest does a serology test for Anaplasmosis which is better. The Ehrlychia test is the best of this group. The other tests cannot be relied upon for varying reasons. Positive results for Babesia, Bartonella and Ehrlichia when they do appear, not only provide evidence regarding these co-infections, but also provide good, indirect evidence of Borrelia infection as well.
The CD57 test is frequently ordered. This is available only through Labcorp. It's value remains controversial. Low levels tend to suggest immune suppression and possible chronic infection. The C3a and C4a complement tests are available also only from Labcorp. They provide clues of inflammation and therefore infection.
Sed rate and CRP are markers of inflammation. They are frequently elevated. When positive they are helpful.
ANA and RF indicate autoimmune issues. These are also frequently elevated and offer further evidence regarding secondary autoimmune effects.
B12 and folic acid are important. Low levels are common and may be associated with co-infections within red blood cells.
Vitamin D levels: OH 25, and Dihydroxy 1,25 levels may indicate evidence of L-form disease and are useful markers.
CBC is important. Low WBC counts may correlate with Ehrlichia and other tick borne infections. Routine chemistries are important to screen for liver function abnormalities and other metabolic issues.
We have been cost effective so far, assuming third party coverage.
If we want better data we must use speciality labs. These labs generally do not participate with insurance plans.
Lyme Western Blots from reference labs like IgeneX and Clongen are very helpful. The yield can be improved by first giving antibiotics and then performing the assays, especially after a Herx response.
Routine Blood PCRs for Lyme have a very low yield and are not cost effective.
Some physicians assume that co-infections are present and treat empirically, especially if serological evidence of Lyme has been obtained.
The next cost effective test is a blood smear. The presence of gram negative rods or cocco-bacillis suggests Bartonella. if confirmation is desired, a DNA extraction with a 16S DNA fingerprint can be obtained. A finding of Babesia on a blood smear would be great, but this is a low yield procedure.
A new 15 species PCR for Babesia and a 20 species PCR for Bartonella is available from Clongen and should be cost effective. The mill labs do serology for B. microti and IgeneX does serology for B. duncani. This gives a decent yield but misses many pathogenic strains. The FISH test for B. microti from IgeneX is a good test, but it adds extra expense and it only tests for one species.
Let me say a word about the C6 Bb ELISA test. Most LLMDS don't do it because of a low yield. First, it is highly specific. A positive result is better evidence than a positive Western Blot. Second, I view numeric index results differently. The 0.9 cutoff is conservative and was calibrated for acute Lyme, not chronic Lyme disease. Levels over 0.3 are very suggestive and levels over 0.4 correlate highly with the Lyme diagnosis. This test is always worth doing. Because it is quantitative it can be monitored over time during the course of therapy. It frequently "seroconverts" after antibiotics have been administered.
In summary, there are many diagnostic lab options. Many co-infections can be diagnosed empirically. You can work with you LLMD to determine which tests are most appropriate and which fit into your budget. It is OK to discus the cost and benefits of the various tests. I think a good physician who trusts his clinical abilities will often be comfortable working with less lab data. The problem remains that even the best tests frequently miss clinically significant infections; so negative results should not be used as a justification to not treat.
Many LLMDS seem to order large panels from specialty labs which cost thousands of dollars. I think a thoutful approach can save patients a lot of out of pocket expense.
Given that TBD (tick borne disease) is suspected, also called LBC (Lyme Boreliosis complex), (Note these terms are replacing the term chronic Lyme disease because of the increasing assumption of a poly-microbial syndrome), one must give careful consideration regarding the use of ancillary laboratory testing.
The first phase of testing is of course the history and physical exam.
As we move into the realm of lab tests the first priority is to document exposure to Borrelia burdorferi, the Lyme spirochete. Most patients have insurance. This means that tests at "mill labs" like Labcorp and Quest are covered. This is usually the starting place. These labs do a mediocre job with serological(antibody) tests, but appear to do a poor job with PCR testing. Don't order the standard Lyme antibody test. This means an ELISA test will be done. We know this is a poor screening test. Order a direct Lyme Western Blot test. This is a better, yet still poor test. It only reports 13/28 bands. Despite this, sometimes we get lucky. Labcorp and Quest will do serological tests for Ehrlichia, Bartonella and Babesia. Labcorp does a PCR for Anaplasmosis which is poor, while Quest does a serology test for Anaplasmosis which is better. The Ehrlychia test is the best of this group. The other tests cannot be relied upon for varying reasons. Positive results for Babesia, Bartonella and Ehrlichia when they do appear, not only provide evidence regarding these co-infections, but also provide good, indirect evidence of Borrelia infection as well.
The CD57 test is frequently ordered. This is available only through Labcorp. It's value remains controversial. Low levels tend to suggest immune suppression and possible chronic infection. The C3a and C4a complement tests are available also only from Labcorp. They provide clues of inflammation and therefore infection.
Sed rate and CRP are markers of inflammation. They are frequently elevated. When positive they are helpful.
ANA and RF indicate autoimmune issues. These are also frequently elevated and offer further evidence regarding secondary autoimmune effects.
B12 and folic acid are important. Low levels are common and may be associated with co-infections within red blood cells.
Vitamin D levels: OH 25, and Dihydroxy 1,25 levels may indicate evidence of L-form disease and are useful markers.
CBC is important. Low WBC counts may correlate with Ehrlichia and other tick borne infections. Routine chemistries are important to screen for liver function abnormalities and other metabolic issues.
We have been cost effective so far, assuming third party coverage.
If we want better data we must use speciality labs. These labs generally do not participate with insurance plans.
Lyme Western Blots from reference labs like IgeneX and Clongen are very helpful. The yield can be improved by first giving antibiotics and then performing the assays, especially after a Herx response.
Routine Blood PCRs for Lyme have a very low yield and are not cost effective.
Some physicians assume that co-infections are present and treat empirically, especially if serological evidence of Lyme has been obtained.
The next cost effective test is a blood smear. The presence of gram negative rods or cocco-bacillis suggests Bartonella. if confirmation is desired, a DNA extraction with a 16S DNA fingerprint can be obtained. A finding of Babesia on a blood smear would be great, but this is a low yield procedure.
A new 15 species PCR for Babesia and a 20 species PCR for Bartonella is available from Clongen and should be cost effective. The mill labs do serology for B. microti and IgeneX does serology for B. duncani. This gives a decent yield but misses many pathogenic strains. The FISH test for B. microti from IgeneX is a good test, but it adds extra expense and it only tests for one species.
Let me say a word about the C6 Bb ELISA test. Most LLMDS don't do it because of a low yield. First, it is highly specific. A positive result is better evidence than a positive Western Blot. Second, I view numeric index results differently. The 0.9 cutoff is conservative and was calibrated for acute Lyme, not chronic Lyme disease. Levels over 0.3 are very suggestive and levels over 0.4 correlate highly with the Lyme diagnosis. This test is always worth doing. Because it is quantitative it can be monitored over time during the course of therapy. It frequently "seroconverts" after antibiotics have been administered.
In summary, there are many diagnostic lab options. Many co-infections can be diagnosed empirically. You can work with you LLMD to determine which tests are most appropriate and which fit into your budget. It is OK to discus the cost and benefits of the various tests. I think a good physician who trusts his clinical abilities will often be comfortable working with less lab data. The problem remains that even the best tests frequently miss clinically significant infections; so negative results should not be used as a justification to not treat.
Many LLMDS seem to order large panels from specialty labs which cost thousands of dollars. I think a thoutful approach can save patients a lot of out of pocket expense.
Sunday, November 2, 2008
Activation of Lyme (and tick borne disease)
A large percent of Lyme and tick borne infected persons are asymptomatic. What percent? That's the 64 thousand dollar question. No one knows. I have seen many patients whose underlying Lyme disease has been suddenly activated; it has frequently been associated with an unrelated infectious disease. I would like to briefly discus three such cases.
An otherwise well woman is given Cipro for a urinary tract infection. Her right knee "blows up" (becomes very swollen with effusion) and becomes very painful. It turns out that the acute arthritis of her knee is due to Lyme disease. Here is my theory: Cipro and related drugs are associated with joint and tendon injury. Perhaps this occurs in patients with underlying, asymptomatic Lyme infection. the person may have Borellia, Lyme bacteria, colonizing the lining of the joint or the tendon sheath involved. The rapid killing of the organisms causes a marked inflammatory response. On could view this as a localized Herxheimer reaction. In this case Lyme arthritis developed only after Cipro was given for an unrelated urinary tract infection.
A teenage girl is diagnosed with acute mono(mononucleosis). She has a fever, sore throat, swollen glands and fatigue. Her exam shows a red throat with exudate(white coating of tonsils) and swollen glands in a typical mono pattern. Her laboratory tests showed a positive mono spot test and atypical lymphocytes on the CBC. The diagnosis of mono was very straightforward. This young woman who had enjoyed good health did not improve in the expected time frame. She developed persistent fatigue, progressive joint and muscle pain, numbness and tingling and brain fog. Further lab testing showed that she had chronic Lyme infection. The patient improved when Lyme disease was treated. Comment: the opposite situation is frequently seen. Patients with Lyme are observed to have high antibody titers of EBV and CMV, viruses associated with mono. Perhaps Lyme related immune suppression allows these chronic viruses to activate and contribute to the overall syndrome.
The last case involves a patient I saw last week. This is the most intriguing case. A 47 year old man is in good health. He has an elevated PSA (prostate specific antibody) test found during a routine physical. A urologist performs a biopsy. After this the patient develops an acute febrile illness. He is admitted to the local hospital for sepsis (blood infection) with E. coli, a colon germ associated with urinary tract infections. By chance, he is treated with IV Rocephin. Instead of improving he gets worse. He develops persistent relapsing fevers, headaches, joint pains, muscle pains, neck pain, brain fog and episodes of confusion. He is referred to me because of the unexplained headaches. His blood smear shows numerous spirochetes in the blood stream. His PCR tests are positive for both Lyme and Babesia. In this case, pre-existent, asymptomatic tick borne disease, is activated and becomes both acute and severe in the presence of Rocephin prescribed for an unrelated E.coli infection. Perhaps the old proverb "let sleeping dogs lie" is relevant here. This patient was unaware of tick borne illness and then became very symptomatic when a roaring Herx was unleashed by antibiotics given for an unrelated infection. This is a current, active case.
An otherwise well woman is given Cipro for a urinary tract infection. Her right knee "blows up" (becomes very swollen with effusion) and becomes very painful. It turns out that the acute arthritis of her knee is due to Lyme disease. Here is my theory: Cipro and related drugs are associated with joint and tendon injury. Perhaps this occurs in patients with underlying, asymptomatic Lyme infection. the person may have Borellia, Lyme bacteria, colonizing the lining of the joint or the tendon sheath involved. The rapid killing of the organisms causes a marked inflammatory response. On could view this as a localized Herxheimer reaction. In this case Lyme arthritis developed only after Cipro was given for an unrelated urinary tract infection.
A teenage girl is diagnosed with acute mono(mononucleosis). She has a fever, sore throat, swollen glands and fatigue. Her exam shows a red throat with exudate(white coating of tonsils) and swollen glands in a typical mono pattern. Her laboratory tests showed a positive mono spot test and atypical lymphocytes on the CBC. The diagnosis of mono was very straightforward. This young woman who had enjoyed good health did not improve in the expected time frame. She developed persistent fatigue, progressive joint and muscle pain, numbness and tingling and brain fog. Further lab testing showed that she had chronic Lyme infection. The patient improved when Lyme disease was treated. Comment: the opposite situation is frequently seen. Patients with Lyme are observed to have high antibody titers of EBV and CMV, viruses associated with mono. Perhaps Lyme related immune suppression allows these chronic viruses to activate and contribute to the overall syndrome.
The last case involves a patient I saw last week. This is the most intriguing case. A 47 year old man is in good health. He has an elevated PSA (prostate specific antibody) test found during a routine physical. A urologist performs a biopsy. After this the patient develops an acute febrile illness. He is admitted to the local hospital for sepsis (blood infection) with E. coli, a colon germ associated with urinary tract infections. By chance, he is treated with IV Rocephin. Instead of improving he gets worse. He develops persistent relapsing fevers, headaches, joint pains, muscle pains, neck pain, brain fog and episodes of confusion. He is referred to me because of the unexplained headaches. His blood smear shows numerous spirochetes in the blood stream. His PCR tests are positive for both Lyme and Babesia. In this case, pre-existent, asymptomatic tick borne disease, is activated and becomes both acute and severe in the presence of Rocephin prescribed for an unrelated E.coli infection. Perhaps the old proverb "let sleeping dogs lie" is relevant here. This patient was unaware of tick borne illness and then became very symptomatic when a roaring Herx was unleashed by antibiotics given for an unrelated infection. This is a current, active case.